Incisional wounding of the skin triggers a series of dramatic events in the epidermal keratinocytes that are located immediately adjacent to the margins of the wound, ultimately leading to complete reepithelialization of the wound by these cells. These events include hyperproliferation of basal keratinocytes, dissolution of cell–cell adhesions, detachment from the basement membrane, lateral migration into the wounded area, invasion and proteolytic degradation of the provisional matrix of the wound bed. In many aspects, the healing response resembles the phenotypic events observed during squamous carcinoma progression, in which normal keratinocytes undergo a malignant conversion to acquire a proliferative, migratory and invasive phenotype. To elucidate the molecular mechanisms underlying the transformation of keratinocytes to a migratory and proteolytic phenotype, we initiated a study of global changes in keratinocyte gene expression during mouse incisional skin wound healing. We used laser capture microdissection, which allows the procurement of pure cell populations from heterogeneous histological samples, to isolate wound keratinocytes that actively migrate through and degrade the provisional matrix of full-thickness incisional mouse skin wounds. For comparison, we isolated nonmigrating keratinocytes distal to the wound edge, as well as keratinocytes from mock-wounded mice, in a similar manner. We isolated total RNA (11–18 ng) from approximately 5,000 keratinocytes and generated complex complementary DNA probes by reverse transcription of the messenger RNA fraction. We then screened cDNA expression arrays to identify the expression pattern of 1,176 mouse genes in the three populations of keratinocytes. Results of the expression studies will be presented and discussed.