The mycotoxin fumonisin B1 (FB1) is an important contaminant of maize and maize-based products. In rodent toxicity studies, FB1 was shown to be hepato- and nephrotoxic, and to induce renal tumors in rats when administered via the diet. Of particular note are the aggressive growth characteristics of FB1-induced tumors with a high potential to metastasize. While genotoxicity does not appear to contribute to FB1 carcinogenicity, it is well established that FB1-mediated disruption of sphingolipid metabolism plays a key role in FB1 toxicity. This review provides an overview on human dietary exposure to FB1, FB1 toxicity and carcinogenicity, and potential mechanisms involved in FB1-mediated tumor formation, with a particular focus on cellular functions of sphingolipids and biological consequences of FB1-mediated perturbation of sphingolipid metabolism.