Accumulating evidence suggests that pituitary tumor transforming gene 1 (PTTG1) is a potential biomarker for cancer malignancy and a cell-cycle regulatory protein. This investigation was performed to address the subcellular localization of PTTG1 and its possible involvement in proliferative skin diseases. In vitro primary-cultured keratinocytes and skin samples from psoriasis, seborrheic keratosis (SK), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) were investigated by immunofluorescence and real-time PCR. In normal skin, PTTG1 is localized predominantly in 10% of basal keratinocytes, while 30-40% in basal and suprabasal psoriatic keratinocytes. PTTG1 mRNA in psoriatic epidermis is about 5-fold more than that in normal one (P<0.01). PTTG1 is localized in cytoplasm in primary-cultured normal and psoriatic keratinocytes, and PTTG1 in HaCaT cells is distributed throughout the cytoplasm of metaphase cells. PTTG1 is seen at both G2 and M phases, and highest PTTG1 expression correlates with highest cyclin B1 expression and highest degree of nuclear pleomorphism at M phase. The positive rate of PTTG1 in SK, BCC, and SCC is about 10%, 20%, and more than 80%, respectively. PTTG1 siRNA, which knocks down the expression of PTTG1, reduced the invasive capacity of A431 cells. In conclusion, PTTG1 is a marker for proliferative skin diseases associated with cell cycle regulation and may aid in detection of aggressive cancers.