Human foreskin epithelial cells were transformed to an anchorage-independent state of growth (in soft agar) and neoplasia (invasion of chick embryonic skin in vitro). Aflatoxin B1, N-methyl-N'-nitro-N-nitrosoguanidine, propanesultone, beta-propiolactone, or ultraviolet absorbance at 254 nm were used successfully as carcinogens. These foreskin epithelial cells, like human foreskin fibroblasts, were readily transformed when treated in S phase but, unlike the transformed fibroblasts, expression of cellular neoplasia did not require an extended period of time in culture. The invasive features of the transformed human epithelial cells in chick embryonic skin in vitro simulated squamous cell carcinoma.