The state-run railway company said the derailment could have been the result of sabotage, fueling fears of terrorism.
The three rear cars of the Nevsky Express went off the tracks in the Tver province northwest of Moscow, the Emergency Situations Ministry said. Russian Railways said that four cars derailed and said 50 people were taken to two hospitals in the area.
Based on reports from officials at the scene, Emergency Situations Minister Sergei Shoigu said 25 people were killed, including two who died on the way to a hospital, and 87 injured. He said 32 people were unaccounted for, but that some or all of them may have survived.
State-run Vesti-24 television showed grainy footage hours after the derailment of a damaged car apparently lying on its side by the tracks. Its reporter called the wreck a "terrible catastrophe," saying he was looking at a "warped" carriage and could see other damaged cars as ambulances drove in and out of the cordoned-off site.
Reporting to a crisis center in Moscow, an officer at the scene said the death toll could rise because five or six bodies were believed trapped under a carraige.
Russian Railways said the cause was not yet determined but one possibility was sabotage, which could mean a bomb or another deliberate action to derail the train and cause casualties. Russian news agencies cited unidentified officials as saying a small crater was found at the site of the wreck, leading to speculation that it could have been caused by explosives.
A bomb blast on the same line in 2007 derailed a passenger train and injured 27 people. Two suspects have been arrested and authorities are searching for a former military officer they believe was behind the blast, but the motive was unclear. An explosion in a bathroom on a Moscow-St. Petersburg train in 1997 killed five people.
The route between Russia's capital and its No. 2 city is heavily traveled by tourists and business people.
The 14-car train was carrying 633 passengers and 20 railway personnel, the emergencies ministry said.
Terrorism has been a major concern in Russia since the devastating wars pitting Chechen rebels against government forces in the 1990s. Violence stemming from those conflicts has repeatedly spread to other parts of Russia in the past decade, including deadly bombings in the Moscow subway and attacks that brought two passenger jets down in 2004.
But Russia has also been plagued by deadly accidents resulting from its deteriorating Soviet-era infrastructure and from negligence.
The derailment occurred near the border between the Novgorod and Tver provinces, about 250 miles (400 kilometers) northwest of Moscow and 150 miles (250 kilometers) southeast of St. Petersburg, authorities said.
Russian news agencies reported that some injured passengers were being taken by train and bus to hospitals in the area and to St. Petersburg for medical attention.
State-run Vesti-24 broadcast live from a modern-looking national crisis response center center in Moscow late into the night as Emergency Situations Minister Sergei Shoigu and Health Minister Tatyana Golikova barked out orders and heard reports from officials at the scene and at nearby hospitals about casualties and the logistics of treating the injured.
President Dmitry Medvedev ordered authorities to help the victims and determine what caused the derailment, state media cited the Kremlin as saying.