Description of clinical cases: Case 1: A 60-year-old female patient was oberved with a single greyish macular lesion on the oral floor. Excisional biopsy was performed and the pathological examination confirmed the diagnosis of amalgam tattoo. Case 2: A 73-year-old male patient was observed with a single brown macular lesion on the hard palate. Excisional biopsy was performed and the pathological examination confirmed the diagnosis of oral melanotic macula. Case 3: A 66-year-old male patient was observed with a single bluish macular lesion on the hard palate. Excisional biopsy was performed and the pathological examination confirmed the diagnosis of blue melanocytic nevi. Case 4: A 72-year-old female patient was observed with a single brown macular lesion on the hard palate. Incisional biopsy was performed and the pathological examination confirmed the diagnosis of oral melanoma. Discussion: The color changes in the oral mucosa may correspond to a great variety of physiological or pathological, benign or malignant and local or systemic entities. The aim of this communication is to demonstrate through clinical cases which oral pigmented lesions are most relevant in the oral cavity. Conclusions: The differential diagnosis of oral pigmented lesions is usually a major challenge to the dentist. A biopsy is a valuable tool in establishing the definitive diagnosis, essential for the implementation of the appropriate therapy. Keywords: Amalgam tattoo, melanotic macula, blue melanocytic nevi, oral melanoma, pigmented lesions, differential diagnosis