Digit regrowth following amputation injury proximal to the first phalangeal joint is not a property of mammalian wound healing. However, the regenerative potential observed in the MRL mouse invites a reexamination of this rule. In this study, healing was assessed in three mouse strains after amputation midway through the second phalangeal bone. Three distinct outcomes were observed though evidence for regrowth was observed only in the MRL mouse. Here, a blastema-like structure was seen along with apparent chondrogenesis, consistent with a histological profile of a regenerative response to injury. Analysis of trichrome staining and basement membrane changes, proliferation and apoptosis indicated that these processes contributed to the formation of new digit tissue. On the other hand, SW and B6 digits did not show evidence of growth with little mesenchymal BrdU incorporation or phosphorylation of H3.