Degradation of basement membranes and extracellular matrix is an essential step in cancer invasion and metastasis. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in this step. The present study was conducted to investigate the levels of MMP-3 and TIMP-1 in serum of patients with malignant melanoma and the relationship to tumor progression and known prognostic parameters. Seventy patients with cutaneous malignant melanoma were investigated. Serum samples were obtained on first admission before any adjuvant and metastatic treatment was given or follow-up of patients. Serum TIMP-I and MMP-3 levels were determined by the solid-phase sandwich ELISA (Oncogene Science Inc.) method. The elevation of serum MMP-3 and TIMP-1 levels between the patients with malignant melanoma and healthy controls were not significantly different (p > 0.05). The serum levels of MMP-3 were significantly different in males and females (p = 0.001) and serum TIMP levels were influenced by age (p = 0.047). Except for the ulceration status of the tumor, serum levels of MMP-3 and TIMP-1 were not related to the known prognostic factors such as tumor histology, localization, stage of the disease, Breslow thickness, Clark invasion, mitosis, TIL, and regression of tumor (p > 0.05). In patients with ulceration positive, the serum levels of MMP-3 were higher (p = 0.04) and TIMP-I were lower (p = 0.008) than those in patients without ulceration. No significant relationship was found between serum levels of MMP-3 and TIMP-1. In conclusion, these results suggest that neither of the serum levels of MMP-3 and TIMP-I could be a good indicator of invasion and metastasis nor can be recommended as a tumor marker in the management of melanoma patients owing to lack of sensitivity and specificity. However, much research still continues in this field and exciting new knowledge will ultimately emerge.