The 57 year-old Chavez, who is seeking re-election in October, vowed to defeat "this new difficulty" just ahead of boarding his flight to Havana.
Chavez arrived at the airport in a caravan along with thousands of supporters, and then, flanked by his two daughters, told the crowd and the TV cameras that he will show a strong will for "this new battle" to "defeat the threat" of the illness.
Chavez underwent surgery and four rounds of chemotherapy in Cuba last summer after cancer was detected in his pelvic region. The government has not said what kind of cancer and has provided few details about his exact condition, and in October Chavez claimed to be cancer-free.
But on Tuesday he said that doctors had detected a new "lesion," and late Thursday he warned that it could be malignant.
"Nobody can say right now that it is another malignant tumor... (but) the likelihood of malignancy is greater than the probability that it is not," Chavez said during an event broadcast on state-run television.
Chavez said the operation could take place Monday or Tuesday.
The South American nation, one of the world's top oil producers, faces a period of uncertainty as it ramps up for what is likely to be the most closely contested presidential election in years.
The cancer scare comes as Chavez faces a strong election challenge from 39-year-old Henrique Capriles, who was chosen as the sole opposition candidate in a presidential primary earlier this month.
Chavez could still appoint a successor to run in his place, the October 7 vote could be delayed, or he could muddle through with a campaign message shifting attention from his health to his left-wing legacy.
The opposition asked that Chavez delegate powers to Vice President Elias Jaua during his absence, but the pro-government majority in the National Assembly rejected the request.
Copyright AFP (Agence France-Presse), 2012