The use of immunohistochemical markers for myoepithelial cells (MEC) is a useful tool in the distinction of benign from malignant epithelial neoplasms. Although their use in breast tumors is well recognized, little is known concerning its application in comparable cutaneous lesions. Using benign cutaneous cystic apocrine lesions as a study model, the aim of this study was to compare 5 immunohistochemical markers [calponin, p63, smooth muscle actin (SMA), cytokeratin 14, and CD10] in their effectiveness to highlight MEC. Cases of apocrine hidrocystoma and cystadenoma (n = 44) were reviewed with a particular emphasis on proliferative features and apocrine change. The MEC staining pattern and the intensity and distribution scores in proliferative (n = 29) and nonproliferative (n = 15) lesions were assessed, and the differences between the 2 groups were statistically analyzed using Fisher exact test. Calponin and SMA stained MEC in the most consistent manner. Being a nuclear stain, p63 was easy to interpret but typically showed discontinuous staining. Cytokeratin 14 not only effectively highlighted MEC but also stained some luminal epithelial cells in an unpredictable manner. Because of prominent background dermal fibroblast staining, CD10 was often difficult to interpret. Only SMA and p63 showed a statistically significant difference in MEC staining intensity scores between the proliferative and nonproliferative groups. Our results show that immunohistological staining for MEC in benign cystic apocrine lesions of the skin is variable. The authors recommend that a panel of markers that includes calponin and p63 be used and highlight the need for awareness of specific caveats associated with individual markers.