Background:Favre-Racouchot syndrome (nodular cutaneous elastosis with cysts and comedones) is a cutaneous disease characterized by coexistence of cysts, comedones and elastotic nodules in actinically damaged skin, typically on the face. Ultraviolet radiation plays a significant role in the development of the disease. Unilateral lesions have been described.Main observation:In this report we present two cases of squamous cell carcinoma arising in a unilateral Favre-Racouchot plaque. Both patients, fair-skinned, elderly, with impaired immune function developed large, deep invasive tumors with perineural extension.Conclusions:Squamous cell carcinomas of large size and prominent invasive growth developing in immunocompromised individuals carry poor prognosis with regard to recurrence rate and metastasis. Manifestations of malignancy as described in this report, indicate the importance of close follow-up of patients with Favre-Racouchot syndrome.