The activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests for melanoma patients. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were carried out. This prospective study included 61 melanoma patients [stage I-II (n=10), stage III (n=14), stage IV (n=37), M1c (n=26) disease], and 50 healthy controls. It included 34 (56%) men, median age 53 years, range 16-88 years. Over half of the patients (54%) were in the metastatic stage and most of them (70%) had M1c. The plasma level of pretreatment blood coagulation tests including DD, F, APTT, INR levels, and PLT counts showed a statistically significant difference between the patient and the control group (P<0.001 for all, but P=0.049 for INR). The levels of INR, DD, F, and PLT counts were higher and APTT was lower in the melanoma group, whereas the PT and PTA levels did not show any significant difference. There was a significant association between PT, PTA, INR, and PLT levels and the age of the patient. Patients with node metastasis in M0 disease had higher levels of PTA and PLT counts (P=0.002 and 0.048, respectively) and lower levels of PT and INR (P=0.056 and 0.046, respectively). The M1c patients tended to have higher plasma F levels (437 vs. 297 mg/dl, P=0.055) than M1a and M1b patients. The 1-year survival rate for all patients was 70%. In association with distant metastasis, advanced metastatic stage (M1c), elevated lactate dehydrogenase, and erythrocyte sedimentation rate, only elevated plasma F levels had a significantly adverse effect on survival among the coagulation parameters (P=0.031). The 1-year survival rates for patients with high and normal F levels were 58 and 88%, respectively. In conclusion, changes in the coagulation-fibrinolytic system are often present in melanoma and elevation in the plasma F level is associated with decreased survival.