The majority of penile cancers and pre-cancerous lesions arise from the squamous epithelium of the glans and inner prepuce, but they may also arise from the penile shaft. In its early or premalignant stage, penile cancers may mimic other benign penile conditions. This can lead to misdiagnosis, delays in treatment, suboptimal outcomes, and increased mortality. Although penile cancers constitute a rare group of premalignant/cancerous lesions, they are of great concern to both urologists and dermatologists due to their indeterminate nature on clinical examination and the potential for misdiagnosis. Prompt diagnosis with a low threshold for biopsy forms a key part of the investigative work-up when clinicians are confronted with any superficial penile dermatosis. In this chapter, we emphasize the differences between benign, premalignant, and malignant superficial lesions and discuss the different treatment modalities used in clinical practice.