Fas (APO-1/CD95) consists mainly of 2 isoforms, membrane-anchored (mFas) and soluble (sFas), both of which can mediate apoptosis through the Fas-signalling process, not only in normal but also in leukemia T-cells. This suggests that aberrant expression of either mFas or sFas may affect the natural history of T-cell neoplasms, such as adult T-cell leukemia (ATL). For studying the tumor biology related to Fas-mediated apoptosis, ATL cells with up-regulated Fas proteins and its mRNAs are convenient and useful for understanding apoptotic oncology as it occurs in nature. Most attention, so far, has been focused on mFas, and little is known about neoplasms from the viewpoint of sFas. Accordingly, we herein review and discuss the biological and clinical implications of sFas in ATL.