ITAR-Tass news agency quoted an unidentified emergency official as saying 22 people were killed and 55 injured. RIA Novosti reported the toll was 21, also citing emergency officials.
Authorities said up to four cars of the express train went off the tracks in an area separating the Novgorod and Tver provinces.
Russian Railways said the cause was not yet determined but one possibility was sabotage, which could mean a bomb or another action that caused the derailment.
