One hundred and two cases of benign sweat gland tumors of the skin were studied for the presence of myoepithelial cells specifically identified by a monoclonal antibody to alpha-smooth muscle actin on paraffin-embedded tissues. The monoclonal antibody gave a positive result in 12 of 12 cases of cylindroma, 14 of 16 cases of spiradenoma, 2 of 2 cases of apocrine tubular adenoma (papillary eccrine adenoma), 5 of 5 cases of apocrine hidrocystoma, 5 of 5 cases of hidradenoma papilliferum, and in 10 of 10 cases of syringocystadenoma papilliferum. Rare myoepithelial cells were detected in only 1 of 10 cases of mixed tumor, apocrine type. There was no immunoreactivity for alpha-smooth muscle actin in eccrine hidrocystoma (2 cases), mixed tumor of eccrine type (2 cases), syringoma (7 cases), hidroacanthoma simplex (1 case), eccrine poroma (14 cases), clear cell hidradenoma (15 cases), and in 1 case of eccrine syringofibroadenoma. Our data support the concept that myoepithelial cells are seen in most sweat gland tumors considered to differentiate toward the secretory coil of the normal sweat gland. In contrast, myoepithelial cells are absent in tumors showing differentiation toward the excretory (ductal) component of the gland.