Background/Aim: A growing body of evidence shows that the differential expression of E domain-related insulin-like growth factor-I (IGF-I) transcripts (IFG-IEa, IGF-IEb and IGF-IEc) in normal and cancerous tissues, implicating specific biological roles for the putative Ea, Eb, and Ec peptides, beyond IGF-I. Herein, we investigated the expression profile of IGF-IEa, IGF-IEb and IGF-IEc transcripts in bladder cancer and compared them with samples from the normal adjacent bladder tissue. Materials and Methods: Biopsies from 46 patients (39 men and 7 women), aged 73.3±10.9 years, were analyzed for the expression of IGF-I transcripts using semi-quantitative real time-PCR (qRT-PCR). Results: The presence of all three IGF-I transcripts was detected in both normal urothelium and bladder carcinomas. The relative expression of the IGF-IEa and IFG-IEb was marginally increased in bladder cancer tissues compared to normal tissue (p〉0.05). In contrast, the expression of the IGF-IEc was significantly decreased in bladder cancer as compared to normal adjacent urothelium (p〈0.05). This specific suppression of IGF-IEc expression was evident and positively correlated with the histological and/or clinical characteristics of an advanced disease, referring to clinical stage, tumor grade and disease recurrence (p〈0.05); however, in situ carcinomas exhibited an increased expression of all IGF-I transcripts. Conclusion: Our data confirm the differential expression of IGF-I transcripts in bladder cancer, revealing a distinct suppression of IGF-IEc. These findings suggest that IGF-IEc expression and putative Ec product may possess discrete biological role in disease progression beyond IGF-I.