Background Cathepsins are a class of proteases that can degrade components of the extracellular matrix. Their role in tumor progression and invasion is well documented. Cathepsin K is a member of this family with strong collagenolytic and elastolytic activity. Objectives To assess and compare the expression of cathepsin k protease in benign (seborrheic keratosis SK), premalignant (actinic keratosis AK), locally malignant (basal cell carcinoma BCC) and invasive cutaneous tumors (squamous cell carcinoma SCC). Patients and methods The study included 45 participants divided into five groups: one control group (9 normal skin specimens) and four case groups (9 patients with SK, 9 patients with AK, 9 patients with BCC and 9 patients with SCC). All skin biopsies were subjected to immunohistochemical stain of cathespin K. Results The epithelial and stromal scores of cathepsin K were significantly higher in all epidermal tumors compared to the control group. Cathepsin K expression was noticed in the benign and premalignant tumors; however it was significantly lower than the invasive ones. Conclusion Cathepsin K has a significant role in epidermal tumor invasion and increased expression is correlated with more aggressive tumors. Cathepsin K inhibitors can be a promising line of treatment of cutaneous tumors.