Prolidase deficiency and solitary mastocytoma of the eyelid are both exceedingly rare. Prolidase deficiency is an inherited connective tissue disorder that has systemic sequelae, such as intractable skin ulceration, poor wound healing, recurrent infections, and intellectual impairment. Cutaneous mastocytoma is an isolated, aberrant cutaneous aggregation of mast cells. A case of an adult with severe prolidase deficiency who developed cutaneous mastocytoma of the eyelid was presented. To the authors’ knowledge, adult-onset solitary mastocytoma of the eyelid has never been reported previously.