Conditional gene targeting using the Cre/loxP technology generally includes integration of a selection marker cassette flanked by loxP recognition sites (floxed) in the target gene locus. Subsequent marker removal avoids possible impairment of gene expression or mosaicism due to partial and total deletions after Cre‐mediated recombination in vivo. The use of deleter Cre mice for in vivo marker removal in floxed connexin43 mice revealed considerable mosaicism, but no selective marker removal. In addition, we noted that several Cre transgenic lines displayed spontaneous ectopic activity, reminiscent of deleter Cre mice, and required the confirmation of cell type‐specific deletion in every individual mouse. When we used myosin heavy chain promoter Cre (αMyHC‐Cre) mice for cardiomyocyte specific deletion, we observed, in addition to cardiomyocyte‐restricted or complete excision, selective marker removal in a subgroup of mice as well. Thus, selective marker removal can be achieved as a byproduct of cell‐type restricted deletion. genesis 38:159–165, 2004. © 2004 Wiley‐Liss, Inc.