The presence and localization of caspase 3, a master enzyme in apoptosis, have been analyzed in tissues of four species of Molluscs: the Bivalves Callista chione and Adamussium colbecki and the Gastropods Helix pomatia and Neobuccinum eatoni. Western blotting and immunocytochemical analyses show that a 32 kDa caspase 3 is present in guts, in gill lamellae and in digestive glands during digestion but not in heart tissue or in resting digestive glands. The enzyme is also found in gonads of both sexes but there are significant differences between Bivalves and Gastropods and between male and female germ cells, especially in late stages of differentiation. In particular, caspase 3 is abundant in Bivalves oocytes and in Gastropods spermatozoa but not in Gastropods oocytes; in Callista spermatozoa it appears only after sea water activation. TUNEL staining and PCNA immunolocalization, carried out on C. chione and H. pomatia tissues, suggest that caspase 3 is primarily associated with degenerative processes in gut, digestive gland and early stage germ cells while in gills, oocytes and mature spermatozoa it is primarily correlated with cell function and/or differentiation. J. Exp. Zool. 319A: 548–559, 2013. © 2013 Wiley Periodicals, Inc.