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Schistosomiasis is one of the most prominent parasite-induced infectious diseases, causing tremendous medical and socioeconomic problems. Current studies have reported on the spread of endemic regions and the fear of development of resistance against praziquantel, the only effective drug available. Among the <i>Schistosoma</i> species, only <i>S. haematobium</i> is classified as a Group 1 carcinogen (definitely cancerogenic to humans), causing squamous cell carcinoma of the bladder, whereas infection with <i>S. mansoni</i> is included in Group 3 of carcinogenic hazards to humans by the International Agency for Research on Cancer (IARC), indicating insufficient evidence to determine its carcinogenicity. Nevertheless, although <i>S. mansoni</i> has not been discussed as an organic carcinogen, the multiplicity of case reports, together with recent data from animal models and cell culture experiments, suggests that this parasite can predispose patients to or promote hepatic and colorectal cancer. In this review, we discuss the current data, with a focus on new developments regarding the association of <i>S. mansoni</i> infection with human cancer and the recently discovered biomolecular mechanisms by which <i>S. mansoni</i> may predispose patients to cancer development and carcinogenesis.