This study aimed to determine if hot ethanol and aqueous extracts from the Fomitopsis cajanderi mushroom species are cytotoxic to human cancer cell lines and modulate TNF secretion by human monocytes. The hot ethanol extract was made via a 2 hour Soxhlet extraction of F. cajanderi fruiting body in ethanol using a cold finger condenser. The hot aqueous extract was made via a 2 hour decoction in water at 100°C. Human MCF7 mammary adenocarcinoma and U-937 histiocytic lymphoma cells were treated with increasing concentrations of extract or solvent controls and were assessed for cytotoxicity by XTT colorimetric assay. Effects of the aqueous extract on TNF secretion by PMA-differentiated, LPS-stimulated U-937 cells were determined by TNF ELISA. Glycosyl content and linkage analysis of the aqueous extract were assessed by the Complex Carbohydrate Research Center (Athens, Georgia, USA). The hot ethanol extract induced concentration-dependent cytotoxicity of MCF7 and U-937 cells, with stronger U-937 tumoricidal effects. The hot aqueous extract was not cytotoxic to MCF7 cells, but had cytotoxic effects on undifferentiated U-937 cells at high concentrations. The aqueous extract, found to contain beta glucans, inhibited TNF secretion by LPS-stimulated U-937 cells in a concentration-dependent manner. Hot ethanol and aqueous F. cajanderi extracts showed differential tumoricidal actions on human cancer cells. The ethanol extract was cytotoxic to the human cancer cells tested. The aqueous extract contained beta glucans reported to be immunomodulatory, and inhibited U-937 TNF secretion. These results warrant further research of F. cajanderi extracts as novel adjunctive anti-cancer and anti-inflammatory agents.