Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy.We have assessed the degree of conservation of a set of canine Bcl-2 familymemberswith the human andmurine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequenceswere analyzed, and their functional interactionswere studied in yeasts.Wefound a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro-apoptotic Bax and Bak and antiapoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systemsbased on canine-derived proteinsmight faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies with canine proteins.