Previous studies have demonstrated the dramatic antitumor activity of sodium 5,6-benzylidene-L-ascorbate (SBA). However, the molecular mechanism of this antitumor action is unclear. We investigated the changes in the fine structures of a human submandibular gland carcinoma cell line, HSG, during the cell death induced by SBA. When HSG cells were incubated for 6 hours with non-cytotoxic concentrations of SBA, changes in the mitochondria, such as the disassembly of cristae and decrease in the electron density, were discrenible. At cytotoxic concentrations, the swelling and vacuolization of the mitochondria became apparent, while the nuclear architecture including the profile and ratio of heterochromatin and euchromatin and thickness of the nuclear membrane were intact. These data suggest that the mitochondria, not the nucleus, may be the target organelle of SBA, and support the ability of SBA to induce non-apoptotic cell death in HSG cells.