Aim of this work was to define the histopathological features of post-surgical panniculitis. Dermal and hypodermal changes will be analyzed in detail, to understand the cascade of events that characterize the tissue response to surgical trauma. Cutaneous re-excision specimens of cases of basal cell carcinoma, squamous cell carcinoma, and melanoma consecutively seen from January 1, 2011 to June 30, 2011 at the Department of Dermatology, University of Pavia, were included in this study. Only the cases in which the first surgical procedure included the subcutaneous fat, were considered. In addition, the time elapsed from the first surgical procedure and the re-excision had to be included in a period of time from one to three months. All the specimens were stained with hematoxylin and eosin. Thirty cutaneous re-excision specimens were studied. Histopathologic examination revealed changes of epidermis, ranging from slight atrophy to moderate hyperplasia. In two cases focal ulceration was seen, with transfollicular elimination of foreign body material. The main dermal changes observed were the: 1) scar with well defined vertical orientation along the dermal suture line; 2) rounded cicatricial areas with radial branching septa of scarring tissue; 3) foreign body granuloma formation; 4) alignment of hystiocytes at the dermo-hypodermal border; 5) traumatic neuromas. The subcutaneous fat changes included: 1) lobular panniculitis with consistent presence of foam cells; 2) striking anisocytosis with pseudocystic degeneration and necrosis of adipocytes; 3) eritrocyte extravasation, mainly at the dermo-hypodermal border; 4) deep seated phlebitis. Post-surgical panniculitis is a lobular foam cell panniculitis characterized by simultaneous dermal and hypodermal changes, expression of the multi-faceted tissue response to a surgical trauma. This type of peculiar lipophagic response puts post-surgical panniculitis into the wider chapter of lipophage tissue response seen in atherosclerosis, glomerulosclerosis and some infectious models such as Mycobacterium tuberculosis and Chlamydia pneumoniae infections. Furthermore it may be seen as a reliable and convenient model for laboratory investigation on foam cell tissue response.