Sebaceous lesions are associated with two syndromes with widespread multisystem disorders and tumors. Linear sebaceous nevus syndrome has been traditionally known as the triad of sebaceous nevus of Jadassohn, seizures, and mental retardation. This syndrome encompasses a much broader spectrum of multisystem disorders, which is explored below. Muir-Torre syndrome is described as the presence of sebaceous tumors or keratoacanthomas with an underlying visceral malignancy. It is caused by mutations in DNA mismatch repair genes. We discuss its relationship with Lynch syndrome and suggest a comprehensive algorithm on how to screen patients with sebaceous neoplasms for Muire-Torre syndrome. We also provide suggested intensive cancer screening guidelines based on recommendations for patients with Lynch syndrome that may also be of value for patients with Muir-Torre syndrome.