Through humoral and cell-mediated mechanisms, the immune system plays a vital role in protecting every organ system. Disorders of the immune system may result in various cutaneous manifestations, including cutaneous malignancies. In patients with immunodeficiency, the risk of development of malignant cutaneous neoplasms is substantially increased. This increased risk may be due to oncogenic viruses that find a suitable microenvironment for tumorigenesis and cancer development. A subset of cutaneous malignancies that develop in patients with immunodeficiency may show aggressive clinical and biological behavior. Here, we report six cases of highly aggressive and deadly cutaneous neoplasms that arose in patients with a known history of immunodeficiency: two cases of Kaposi sarcoma in patients with immunosuppression due to human immunodeficiency virus infection; a case of Merkel cell carcinoma and a case of squamous cell carcinoma (SCC) in patients receiving immunosuppressive drugs after organ transplant; a case of multiple cutaneous tumors, including invasive melanoma, SCC, and sebaceous carcinoma, in a patient with hypogammaglobulinemia and a history of organ transplant; and a case of basal cell carcinoma and melanoma in situ in a patient with primary immunodeficiency.