The effects of ethanol extracts from four species of mushroom fruiting bodies, mushroom spores and mushroom cultured broth, were assessed for modulation of cell proliferation and apoptosis in murine skin carcinoma cells (CH72) and non-tumorigenic epidermal cells (C50). While extracts from mycelia of Grifola frondosa, Ganoderma lucidum, Hericium erinaceus, or from spores of G. lucidum exerted little, if any, effect on proliferation, the ethanol-soluble extract of Lentinula edodes (L. edodes) significantly decreased cell proliferation of CH72 cells. There were no changes in the proliferative response of the non-tumorigenic keratinocyte cell line, C50, to any of the mushroom extracts tested. To analyze cell proliferation and apoptosis, fluorescent DNA-microscopy with ethidium bromide and acridine orange staining of cells revealed L. edodes reduced cell proliferation and induced apoptosis in time- and dose-dependent manners in carcinoma cells but had no effect in non-tumorigenic cells (C50). Cell cycle analysis demonstrated that L. edodes extract induced a transient G(1) arrest, with no changes observed in the non-tumorigenic cells (C50).