But Nibali says the sport has changed, doping cases have become rare, and "this theme belongs to the past."
The Italian has had a praiseworthy, almost unbreakable lock on the yellow jersey, yet he will be looking over his shoulder more on Friday. The great race enters two days in the Alps that feature uphill finishes, starting with the hardest climb that the peloton has faced so far.
Off the roads, Nibali said he expected questions about doping, a scourge of much of the last generation, for whom performance-enhancers such as blood-booster EPO or human growth hormone, and methods like blood-doping were common.
Many cycling experts say the sport has greatly cleaned up its act. On Thursday, the Sky team, which has won the last two Tours, sacked British cyclist Jonathan Tiernan-Locke after he was banned for an irregular biological passport. He was not a Tour rider, but few would say the Tour peloton was totally clean.
Doping's shadow remains at the Tour, among team staffers, and even a rider or two.
Nibali's team, Astana, was kicked out of the 2007 Tour after its star rider Alexandre Vinokourov tested positive for banned blood transfusions. He served his ban, returned to racing, and won gold at the London Olympics. Vinokourov is now Astana's general manager.
Rider Michele Scarponi who, like Nibali, won the Giro d'Italia and was racing in this Tour, was given a three-month ban in 2012 for seeing banned physician Michele Ferrari, a longtime adviser of Lance Armstrong.
Nibali says Astana has changed.
"I've chosen Astana for the possibility to build a group that I can trust to bring me at a competitive level for important races like the Giro, the Tour and the (Spanish) Vuelta," he said.
"There have been many mistakes in cycling in the past, by many riders, but they belong to the past," Nibali said. "We now have a biological passport, out-of-competition controls, controls at home ...
"Nobody can say that cycling hasn't changed. Nowadays, there is an isolated case. There's always the possibility that an idiot does something stupid ..."
Nibali, a native of Messina, Sicily, nicknamed the "Shark of the Strait" after the Strait of Messina, is trying to become only the sixth rider in history to win all three Grand Tours of France, Italy and Spain. He would also be the first Italian to win the Tour since Marco Pantani in 1998. The late Pantani was convicted in Italy of doping offences during his career.
Giuseppe Martinelli, a cycling guru who worked with Pantani for years before they fell out, is an Astana manager.
"Thanks to him," Nibali said of Martinelli through a translator, "I became closer to the Astana team that has invested a lot in an Italian group in order to regain credibility."
To succeed Pantani, Nibali is keeping an eye out on other race contenders: Richie Porte of Australia trails by 2 minutes, 23 seconds, and Alejandro Valverde of Spain was third, 2:47 back.
The mostly flat 185.5-kilometre (115.5-mile) course from Bourg-en-Bresse to Saint-Etienne in southeastern France was well suited for a possible sprint finish and that's how it was won by Alexander Kristoff, a Norwegian specialist with Katusha.
American rider Andrew Talansky pulled out before the stage due to back pain from two previous crashes. A day earlier, the Garmin-Sharp leader rode for hours and finished last.
Stage 13 will put riders' legs under the most strain yet. The 197.5-kilometre (123-mile) trek begins in Saint-Etienne and will crescendo: It first covers a mid-sized climb and the Category 1 Palaquit pass, and finally an 18-kilometre (12-mile) ascent to Chamrousse — one of cycling's hardest climbs.
"I'm sure our rivals will try to attack but on the other hand, if I can gain some seconds, I'll go for it," the race leader said. "I'll have to evaluate the strength of my adversaries and consider every race situation."
The race has 10 more days.