Squamous cell carcinoma (SCC) can present as a rare complication of longstanding hidradenitis suppurativa (HS) lesions. Limited data exist on characteristics and outcomes of SCC development within HS lesions. The purpose of this review is to conduct a literature review of previously reported cases of SCC development in pre-existing HS lesions. EMBASE and MEDLINE searches were conducted in OVID on June 25, 2020, to yield 59 studies. Of the 95 patients (mean age: 52.9 years) who developed a total of 122 SCCs within HS lesions, the majority were males (77.9%, n = 74/95). The most common sites of SCC were the gluteal region (47.5%, n = 58/122), the perianal region (18.9%, n = 23/122), and the genitals (13.9%, n = 17/122). The mean duration between HS onset and SCC development was 25.5 years. Of the patients that had outcomes reported, 54.0% (n = 34/63) experienced SCC metastasis, 43.1% (n = 28/65) experienced SCC recurrences, and 58.7% (n = 44/75) experienced a mortality outcome. The most common documented reasons for death included metastasis (34.1%, n = 15/44) and sepsis (13.6%, n = 6/44). Patients with longstanding HS lesions can develop SCCs with a high rate of metastasis and mortality. Thus, chronic HS lesions, especially in the gluteal, perianal, genital, and perineal regions, should be monitored regularly for timely SCC diagnosis and management.