Objective: To evaluate a store-and-forward teledermatology system aimed at the routine triage of patients with skin cancer. Design: A multicenter, longitudinal, 4-phase, descriptive and evaluation study of a referred sample of patients attended through teleconsultation between March 2004 and July 2005 (n = 2009). Clinical and dermoscopical examination and histopathological study were considered the gold standard. Setting: A skin cancer unit of a public university hospital and 12 primary care centers in southern Spain. Patients: The study population comprised patients with circumscribed lesions fulfilling at least 1 of the following criteria: changes in ABCD criteria (asymmetry, border irregularity, color variegation, and diameter > 6 mm), recent history, multiple melanocytic lesions, symptoms, and/or patient's application for surgical treatment and concern about moles. Interventions: Diagnosis, diagnostic category (malignant lesions, high-risk lesions, benign lesions, special lesions, and other lesions), diagnostic confidence level on a 3-point scale, and management decision (referral vs; non-referral) were listed after the evaluation of each teleconsultation. A face-to-face evaluation and biopsy of selected patients were performed. Main Outcome Measures: The filtering percentage, as the percentage of patients not referred to the face-to-face clinic, as well as waiting intervals and pick-up or skin cancer detection rates were evaluated as effectiveness indicators. Reliability measures (kappa agreement), accuracy, and diagnostic performance indicators (validity) were also evaluated. Results: The filtering percentage was 51.20% (95% confidence interval [CI], 49.00%-53.40%). The waiting interval to attend the clinic was 12.31 days (95% Cl, 8.22-16.40 days) through teledermatology and 88.62 days (95% Cl, 38.42-138.82 days; P <.001) for the letter referral system. Pick-up rates were 2.02% (95% Cl, 1.10%-2.94%) for malignant melanoma and 27.94% (95% Cl, 24.98%-30.90%) or 1:3.71 for patients with any malignant or premalignant lesion. Intraobserver agreement was kappa=0.91 (95% Cl, 0.89-0.93) for the management decision and kappa=0.95 (95% Cl, 0.94-0.96) for the diagnosis. Interobserver concordance was kappa=0.83 (95% Cl, 0.78-0.88) for the management decision and kappa=0.85 (95% Cl, 0.79-0.91) for the diagnosis. Accuracy was kappa=0.81 (95% Cl, 0.78-0.84). Sensitivity was 0.99 (95% Cl, 0.98-1.00);specificity, 0.62 (95% Cl, 0.56-0.69); pretest likelihood, 0.42 (95% Cl, 0.37-0.47); positive posttest likelihood, 0.65 (95% Cl, 0.61-0.69); and negative posttest likelihood, 0.01 (95% Cl, 0.00-0.05). Conclusion: Store-and-forward teledermatology has demonstrated in this series to be an effective, accurate, reliable, and valid approach for the routine management of patient referrals in skin cancer and pigmented lesion clinics.