Background/Aim: Multiple primary malignant tumors are common in patients with renal cell carcinoma. However, reports on the factors that can identify patients with a risk for subsequent primary malignancies have been lacking. This study aimed to investigate whether myoferlin expression can be used as a potential marker to predict subsequent primary malignancies in patients with clear cell renal cell carcinoma (ccRCC). Materials and Methods: We evaluated the relationship of subsequent primary malignancies with clinicopathological factors and myoferlin expression in 152 patients with ccRCC, and we analyzed the strength of the association with myoferlin expression. Results: The development of subsequent primary malignancies exhibited significant correlation with patient age (p=0.029), sex (p=0.015), T stage (p<0.001), and myoferlin expression (p=0.017). Furthermore, myoferlin hyperexpression was determined as an independent risk factor for developing a subsequent primary malignant tumor in patients with ccRCC (odds ratio(OR), 2.485, 95% Confidence Interval(CI)=1.052-5.870, p=0.038). Conclusion: Myoferlin hyperexpression can be a useful marker for predicting the development of subsequent primary malignancies in patients with ccRCC. Multiple primary malignant tumors are generally defined as two or more discrete cancers that are not the result of metastasis or recurrence, but are independent of each other (1, 2). According to the International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC), one site is regarded as multiple primary malignancies (IARC 2004), not a single tumor of different parts of one site, and a 6-month period is recommended to distinguish between synchronous and metachronous multiple primaries (3). Previous reports have shown that multiple primary malignant tumors are more common in patients with urogenital cancer, and a much higher prevalence of multiple tumors is associated with renal cell carcinoma (RCC) (4, 5). Moreover, Beisland et al. (2) have suggested that patients with RCC should be followed-up with examinations that are more general, due to their increased risk of developing other subsequent primary malignancies. However, little is known regarding the factors that can identify patients with a risk for subsequent primary malignancies. Myoferlin is a member of the ferlin family, and it has been associated with cell membrane repair (6). Myoferlin is expressed in muscle cells and is involved in musculopathy (7). During the embryonic development of muscle or the regeneration of mature muscle cells following damage, myoblasts come together and form large syncytial myofibers (8). Myoferlin is highly expressed during myoblast fusion (8), however, the physiological functions of myoferlin remain to be determined (6). Myoferlin hyper-expression has been studied in many cancers, such as gastrointestinal and hepatobiliary cancers, as well as in cancers of the female reproductive organs (9). Moreover, several reports have shown that myoferlin hyperexpression c...