We found 16 CD56+ cases (29.6%) among 54 acute myeloid leukemia (AML) patients; they showed significantly frequent cutaneous involvement compared to CD56- cases (43.8% vs. 15.8%, p < 0.05). Four of the CD56+ AML cases with specific skin manifestations were reviewed histologically. In all cases, cutaneous leukemic cells were seen in the dermis and subcutaneous tissue with accentuation around the adnexa/nerve, but sparing the epidermis. In addition, angiocentric/angiodestructive and prominent cohesive tumor cell growth were seen in two cases, respectively. These findings suggest that the expression of CD56 may often be associated with the cutaneous involvement in AML, and that the above histological findings should remind us of the possibility of specific skin manifestations in CD56+ AML.