<i>Background:</i> Successful treatment of melanoma depends directly on early diagnosis. Such a diagnosis is based on clinical examination and dermatoscopy. Recently, automated instruments for melanoma detection are under development. <i>Objective:</i> To prospectively evaluate the diagnostic possibilities provided by clinical and dermatoscopic examinations and by a computerized telespectrophotometric system (TS). <i>Methods:</i> The study involves a consecutive series of 298 patients with 313 cutaneous pigmented lesions (66 melanomas and 247 non-melanoma lesions). Each lesion was subjected to the triple diagnostic evaluation, before surgery. Results were expressed in terms of sensitivity and specificity of each kind of evaluation. <i>Results:</i> Clinical evaluation had sensitivity and specificity values of 86 and 77%, respectively, whereas dermatoscopy gave corresponding values of 91 and 74%. TS assessment resulted in a sensitivity of 80% and a specificity of 49%. Differences between clinical and dermatoscopic diagnoses lacked statistical significance (p = 0.22), whereas there was a significant difference comparing both clinical and TS evaluations (p < 0.01) and dermatoscopic and TS evaluations (p < 0.01). Combining clinical and dermatoscopic evaluations, a sensitivity of 97% was achieved. Addition of TS has not changed this figure. <i>Conclusions:</i> Results of this study confirm and stress the importance of dermatoscopy in the diagnosis of melanoma. Clinical evaluation coupled with dermatoscopy can be considered the cornerstone of such a diagnosis. Although TS is able to achieve interesting results, at present it cannot significantly compete with any of the other tested methods.