The Serbia international was withdrawn after 17 minutes of Sunday's derby meeting with Genoa, which ended 1-1 at the Stadio Luigi Ferraris, and medical examinations on Monday have confirmed the extent of the damage.
A statement published on sampdoria.it read: "Nenad Krsticic, accompanied by club doctor Amedeo Baldari, underwent an MRI scan at Laboratorio Albaro in Genoa this morning.
"The tests showed tears to the taliofibular ligament, calcaneofibular ligament and to the joint-capsule of the left ankle.
"The midfielder will be observed over several days of immobility and, after re-evaluation from orthopaedic consultant Professor Claudio Mazzola, we will decide whether to proceed with conservative treatment or with surgery."
The 22-year-old, who moved to Liguria from OFK Beograd in 2008, has made 25 league appearances for Samp this season, scoring one goal in a 2-2 draw at Fiorentina.
Krsticic was diagnosed with Burkitt's lymphoma, a form of blood cancer, in December 2008 but made a full recovery to establish himself as Samp's playmaker alongside Pedro Mba Obiang.
He then played his part as the Blucerchiati reached the top flight through the Serie B play-offs last season before earning his first cap for Serbia in February during a friendly match against Cyprus.