: The primary eye care practitioner assumes an important role in clinical decisions involving the differentiation between malignant and nonmalignant pigmented lesions. A misdiagnosis may have profound consequences on patient management and visual or life prognosis. However, information on these lesions, particularly their appearance using advanced imaging, is fragmented throughout the literature. The purpose of this review is to describe these features in detail, so that the implications of this information on clinical practice are more readily apparent. Clinically relevant descriptions of pigmented lesions of the retinal pigment epithelium using traditional and advanced imaging modalities in the literature were collated and integrated with findings from patients seen at the Centre for Eye Health. The information was then organized and tabulated. Finally, a flow diagram was created to be used as a clinical reference in the differential diagnosis of pigmented lesions of the retinal pigment epithelium.