We report a case of a middle-aged male patient with a diffuse large mixed infiltrating angiolipoma on the back with venous malformation that grew from the age of 3 years. We discussed the design of the surgical flap for this large lipoma, observed its blood supply using SPY, and screened for possible causative genes, FCGR2A, BMP5, MUC2, and KRTAP4-9. To date, no invasive lipomas of this size and duration have been reported.