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The separation between epidermis and dermis occurs at the basement membrane zone, located just inferior to the basal cell keratinocytes.

The outer layer or epidermis is made primarily of keratinocytes but has several other minor cell populations.

These cells reside in the skin for an extended time and respond to different stimuli, such as ultraviolet radiation or topical steroids, which cause them to migrate out of the skin.[5] The dermis is largely composed of an extracellular matrix.

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Overall, 10% of leukemias and lymphomas have prominent expression in the skin.[6] Epidermal appendages are also found in the dermal compartment.These are derivatives of the epidermal keratinocytes, such as hair follicles, sweat glands, and the sebaceous glands associated with the hair follicles.Figure 1 is a simple diagram of normal skin structure.It also indicates the major cell types that are normally found in each compartment.A tendency for superficial necrosis has resulted in the name .[3] Some debate remains about the origin of SCC; however, these cancers are likely derived from epidermal stem cells associated with the hair follicle.[4] A variety of tissues, such as lung and uterine cervix, can give rise to SCC, and this cancer has somewhat differing behavior depending on its source.

Even in cancer derived from the skin, SCC from different anatomic locations can have moderately differing aggressiveness; for example, SCC from glabrous (smooth, hairless) skin has a lower metastatic rate than SCC arising from the vermillion border of the lip or from scars.[3] Additionally, in the epidermal compartment, melanocytes distribute singly along the basement membrane and can undergo malignant transformation into melanoma.These structures are generally formed in the first and second trimesters of fetal development.These can form a large variety of benign or malignant tumors with diverse biological behaviors.Melanocytes are derived from neural crest cells and migrate to the epidermal compartment near the eighth week of gestational age.Langerhans cells, or dendritic cells, are another cell type in the epidermis and have a primary function of antigen presentation.The bottom layer is formed of basal keratinocytes abutting the basement membrane.