Skin cancer is the most common cancer in the United States of America, including melanoma and non-melanoma skin cancer. Malignant melanoma, being ranked as the fifth most common cancer within the US shows a yearly incidence of 73,870 cases and remains the most aggressive form of all skin cancers with a mortality rate of 2.7 per 100,000 [1,2]. Fortunately, over the last decade melanoma treatment options have tremendously improved. Progress in areas such as immunotherapy and targeted therapies has lead to increased melanoma survival rates, rising from 82% (1975-1977) to 93% (2004-2010) [3]. In consequence, the cost of skin cancer treatments, specifically for melanoma treatments increased from an average annual total cost of $864 million in 2002 to $3349 million in 2011 [4].

Non-melanoma skin cancer (NMSC) is the most common cancer among Caucasian populations worldwide. More than 1 million new NMSCs are diagnosed each year, making it the most common cancer in the United States. Basal cell carcinomas (BCCs) account for about 80% of NMSCs, and most of the remainder are squamous cell carcinomas (SCCs) [1]. The treatment of advanced-stage NMSCs is challenging as surgical excision becomes impossible. Recent advances in the treatment of these tumors include targeted molecular therapies against epidermal growth factor receptor (EGFR) and hedgehog signaling pathway.

Nevus spilus (NS) is usually the term given to a pigmented skin lesion, either congenital or acquired, consisting of a large light tan patch, containing macules or papules. Usually, these superimposed lesions are numerous, small circumscribed, dark brown in color, flat or slightly raised. Nevus spilus can be seen anywhere on the body surface, but the most common location is on the chest and upper limbs. NS was first described by Burkley in 1842 as evenly pigmented patches and Ito and Hamado in 1952 were the first to apply the term NS to speckled lesions. For a long time, NS was believed to be a benign lesion. However, more than one case of melanoma arising in NS has been published. As a rule, NS is not considered a precursor of melanoma, but to this day, despite the wide range of publications, it is still necessary to clarify the relationship between NS and melanoma, in terms of the risk factors of turning malignant. We will describe the clinical features, the evolution and the management of NS, in view also of the recent genetic findings.