In vivo studies using epidermal-specific TC-PTP knockout mice revealed that loss of TC-PTP significantly reduced 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis and increased TPA-induced cell proliferation mainly through the regulation of STAT3 and AKT phosphorylation, which resulted in enhanced skin cancer formation during DMBA/TPA skin carcinogenesis. Here, STAT3 is linked to skin cancer.