Objective: The aim of this study was to evaluate the significance of serum tenascin-C levels in the diagnosis, treatment, and monitoring of small round blue cell tumors. Materials and methods: Forty patients and 30 healthy children (control group) were included in this prospective study. Serum tenascin-C levels were measured from blood drawn at the time of diagnosis, at the 3rd and 6th months of treatment, and at 3 months following the completion of treatment. While serum tenascin-C levels were measured a total of 4 times in the patient group, they were measured just once in the control group. Results: Each of the four measured serum tenascin-C levels in the patient group was significantly higher than that of the control group (p=0,013, p=0,009, p=0,011 and p=0,015, respectively). However, when the patient group was categorized into subgroups, only those with Wilms tumor had a significantly higher serum tenascin-C level at the time of diagnosis than did the control group (p=0,026). Conclusion: While larger, more thorough studies are needed, our data suggest that tenascin-C may be useful in the differential diagnosis of certain specific tumors, such as the Wilms tumor.