In a short but brutal 139km stage that featured snow-covered ascents of both the Gavia and Stelvio passes, Movistar's Quintana finished ahead of fellow escapees Ryder Hesjedal (Garmin-Sharp) and Pierre Rolland (Europcar) to take the spoils.
Omega Pharma-Quick Step's Uran finished more than four minutes down and now trails Quintana by 1:41 in the general classification, with Australian veteran Cadel Evans (BMC) dropping to third place at 3:21.
Frenchman Rolland rose to fourth place on GC, 3:26 behind Quintana, despite fading on the steep 14% gradient ramp near the summit of the final climb of the day.
But the crowning of the race's fifth different maglia rosa since the start of the 97th edition in Belfast did not come without controversy, however, with Quintana's initial attack coming on the treacherous descent of the Stelvio which many teams and riders apparently believed to have been neutralised.
With heavy rain and sleet pouring down on the peloton, a crackled announcement on race radio had reportedly announced the neutralisation of the descent.
But with escapee Dario Cataldo (Sky) setting the race alight by riding clear near the summit of the Stelvio and radio reception largely unpredictable, confusion reigned on the long 30km drop to the valley.
A chasing group including Quintana, Rolland and Hesjedal broke clear of the maglia rosa group of Uran during the dangerous downhill, arriving at the foot of the Stelvio with a two minute advantage over the other race favourites.
Isolated and without any team-mates, Uran had to rely on the Tinkoff-Saxo team of Poland's Rafal Majka to lead the chase in the approach to the third and final climb of the day, the "new" climb of Val Martello, making its first appearance on Italy's premier stage race.
With the sun now coming out after what had been an utterly miserable opening two-thirds of the stage, Cataldo held a lead of 1:20 over the Quintana chasing group and three minutes over the Uran group as he rode onto the decisive climb.
Quintana and Rolland rode clear of their fellow escapees before Hesjedal, the 2012 Giro winner, found something in reserve and managed to scramble back onto their wheels. Once caught, Cataldo gamely held on for a couple of kilometres before predictably fading.
It was Rolland who first cracked when the leading trio hit the steepest section of the climb around 5km from the finish. Hesjedal rallied but always looked on the back foot - and when the road entered a twisted, hairpined section inside the final kilometre referred to as the 'cobra' by the Italian press, Quintana danced clear on the pedals towards the summit.
Runner up in last year's Tour de France, Quintana crossed the line eight seconds clear of the impressive Hesjedal, with a gasping and grimacing Rolland taking third place 1:13 down.
Back with the other main contenders, Dutch youngster Wilco Kelderman (Belkin) had attacked on the 14% ramps to drop the struggling pink jersey. Kelderman took fourth place at 3:32, a handful of seconds ahead of Italian pair Domenico Pozzovivo (Ag2R-La Mondiale) and Fabio Aru (Astana).
Uran could only take ninth place, 4:11 down on Quintana, crossing the line in the wheel of another Colombian - Sebastian Henao (Sky) - and a few seconds behind Majka. Evans completed the top ten when he trundled home almost 40 seconds later.
Majka dropped to fifth place in the overall standings ahead of Aru, Pozzovivo and Kelderman. Canada's Hesjedal entered the top ten and will lament the opening day crash that caused his Garmin-Sharp team to concede so much time in the Belfast team time trial.
TEN-MAN GROUP: Despite the grim weather, Robinson Chalapud of team Colombia attacked towards the summit of the first climb of the day, the Gavia, to take maximum points ahead of compatriot Julian Arredondo, the blue jersey from Trek Factory Racing.
Italian veteran Franco Pellizotti caught and passed Chalapud on the wet descent before a group of nine riders finally came together on the flat section ahead of the 2,758-metre Stelvio.
Pellizotti was joined by his Androni-Giocattoli team-mate Diego Rosa, Alexis Vuillermoz and Hubert Dupont (both Ag2R-La Mondiale), Chalapud and Jarlinson Pantano (both Colombia), Robert Kiserlovski (Trek Factory Racing), Dario Cataldo (Sky) and Przemyslaw Niemiec (Lampre-Merida).
Frenchman Alexandre Geniez (FDJ) caught the leaders after the first dozen of the famous 48 hairpin bends of the demanding Stelvio pass - by which time the main pack was closing in. Cataldo launched his solo attack a few kilometres from the summit to take the Cima Coppi prize for the rider first over the highest point of the race.
NEUTRALISATION CONFUSION: A crackled message on race radio seemed to indicate that the descent of the Stelvio had been neutralised - an announcement repeated on the official Giro d'Italia Twitter feed.
But it soon became clear that this piece of information has not reached all the team cars, with Cataldo for one stretching what had been a mere 30-second gap going over the summit to a two-minute advantage on the descent.
There was more confusion with the poor quality of television images, which showed the pink jersey of Uran seemingly taking things easy on each of the sinuous bends. Meanwhile, a cluster of riders had opened up a gap, including Quintana and his Movistar team-mate Gorka Izagguire, Europcar's Rolland and Romain Sicard, Garmin's Hesjedal and Matteo Rabottini of Neri Sottoli.
All of a sudden, we had a serious race on our hands: Uran's pink jersey very much under threat with just one final climb left on the horizon. The rest is history - although the debate as to just what went wrong with the official race communications will no doubt continue.
That the outcome of a stage should be affected by such a lapse is cause for concern. No official flag had been waved by a commissaires car - and the waters were further muddied when the original Tweet that announced the neutralisation was deleted and replaced with the updated news that the descent had not been neutralised.
BIG WINNER OF THE DAY: Nairo Quintana, who now has a commanding hold on the maglia rosa with five days remaining. Although it remains to be seen how much Tuesday's ride took out of a body notoriously prone to illness.
BIG LOSERS OF THE DAY: Rigoberto Uran, who will struggle to take back time from a rider who has looked much more composed in the mountains than himself over the previous few stages.
KEY MOMENT: The misunderstood or miscommunicated announcement that the Stelvio descent had been neutralised, which essentially gave Quintana a two-minute advantage going onto the final climb. If there's one rider in the peloton who doesn't need such a handicap, it's Quintana.
TALKING POINT: Can anyone be to blame for the neutralisation fiasco bar the race organisers? And given the horrendous conditions, should the stage have gone ahead at all in the first place?
COMING UP: The 208km stage 17 from Sarnonico to Vittorio Veneto has been billed as a chance for the sprinters to have a final dig ahead of Trieste - but with a rolling parcours that includes three Cat.4 climbs, it may well be one that suits a break.
- Sports & Recreation
- Pierre Rolland
- Ryder Hesjedal
- Dario Cataldo
- Cadel Evans