The Harlequins fly-half has handed England a major injury scare after he left training on crutches on Monday. Smith pulled up while jogging during a session in Girona, Spain, where England have been preparing for the Six Nations since last week. He had been pushing for start at No10 against Italy, but is now a major doubt.
England hope Smith has avoided serious injury, but will now be made to wait on the results of scans. Former captain Owen Farrell's absence leaves the No10 shirt to be filled, and Smith had been hoping to get the nod.
England already have a lengthy injury list that includes Anthony Watson, Luke Cowan-Dickie, George Martin and Nick Isiekwe. Should live-wire Smith miss out, England will turn to either veteran George Ford or new boy Fin Smith.
Sale's vastly experienced Ford would be the tried and tested option, while Northampton's uncapped Smith has been in excellent form and is ready for the Test step-up.
Saints' George Furbank could provide an option at 10 were England pressed, but the 27-year-old is far more at home in the back three.
Saints centre Fraser Dingwall should be in strong contention to feature in Rome, with Ollie Lawrence sidelined with a hip injury. Henry Slade has a fine chance of being involved, too, having been drafted back in after being omitted from the World Cup squad.