The skin is the largest and most visible organ in the human body, and it serves as its interface with the external world. These unique features mean the integumentary system has a multifaceted and complex role in the expression of cancer. Dermatological manifestation and related conditions are often the first heralds of internal malignancies. This can take the form of direct malignant invasion in the skin, which is seen most commonly in colon, lung, sarcoma, and in women only, breast and ovary. However, direct invasion is far from the only dermal manifestation of cancer. Malignancies also lead to a spectrum of hormonal, neurological, paraprotein, and hematological disturbances, which frequently manifest as cutaneous paraneoplastic phenomena. These conditions can present with hyperkeratotic, inflammatory, and bullous skin findings that can aid in diagnosis of occult malignancies. Finally, this chapter will address genodermatoses and other inherited skin conditions with highly malignant association. For each of these pathological entities, we will focus upon the epidemiology, dermatological exam, and histopathology needed for diagnosis. Therapeutic management will be touched upon but not explored in depth as each entity is complex and frequently variable in their clinical and therapeutic course requiring a multidisciplinary approach to manage. However, management cannot occur without the prompt recognition and referral of these conditions to appropriate specialized facilities by primary care providers and general dermatologists.