Melanoma inhibitory activity (MIA) protein was identified in significant quantities in primary and metastatic malignant melanomas, where it has an important role in promoting tumor development and progression. Our hypothesis was that MIA serum level will be elevated in patients with metastases or local spreading of the disease before any symptom of such progression is clinically apparent. We compared MIA serum levels in two groups of patients with primary melanoma; those with positive as opposed to those with negative sentinel lymph nodes. In addition, MIA serum levels were studied in two control groups; patients with dysplastic nevi and patients with basal cell carcinoma. A blood sample was obtained from each patient included in the study and MIA levels were assessed using standard enzyme-linked immunosorbent assay method. Patients with histologically positive sentinel lymph nodes, meaning that tumor cells were found in the lymph nodes, had much higher mean MIA values than any other patient group considered in this study. With mean value of 14.53 ng/ml, it was almost twice as high as mean MIA value in patients with histologically negative sentinel lymph nodes (7.32 ng/ml) and more than twice as high than any of the two control groups (P<0.001). However, neither the classification by Clarke nor the classification by Breslow could be used to distinguish patients with positive sentinel lymph nodes from those with negative sentinel lymph nodes. In our opinion, MIA serum level is the ideal test for screening the tumor spread to sentinel lymph nodes.