Abstract : <p>Tumor associated macrophages (TAMs) and COX-2 has been reported in association with tumorigenesis, invasion, angiogenesis and metastasis of non-melanoma skin cancer (NMSC). In this study, we used immunohistochemistry on a total number of 30 cases to study histomorphological spectrum and investigate density of TAMs (CD 68) within or at the periphery of tumor along with COX‐2 expression in a series of metastatic tumors of skin i.e. squamous cell carcinoma, basal cell carcinoma and sebaceous cell carcinoma. The maximum patients (33%) were seen in fifth decade with predilection of male gender (60%). The mean age (years) for basal cell carcinoma, squamous cell carcinoma and sebaceous cell carcinoma were 65.59 &plusmn; 8.02, 61.17 &plusmn; 22.95 and 55.00 &plusmn; 0 respectively. Cheek (20%) was more commonly involved site with ulcer (43%) as most common presentation. A significant statistical correlation was found with respect to lesion size (p 0.02) and sun exposure (0.027). Maximum patients were of BCC while maximum association with sun exposure and expression of TAM and COX-2 immunostaining were observed in BCC. In this study, almost 80% and all cases of NMSC simultaneously showed significant expression of COX-2 and TAM (CD 68) respectively but no statistical correlation was found between the various NMSC histological types and differentiation of squamous cell carcinoma as p value was &gt;0.05. Conclusions: We can conclude that both COX-2 and TAM (CD 68) may play role in the development of NMSC as maximum cases showed positivity for both the markers.</p>