Chromosomal rearrangements resulting in the formation of fusion genes are common events in carcinogenesis. There are more than 440 known fusion genes found in both malignant and benign tumors. The mechanism of transcription induced chimerism (TIC) contributes to fusion transcripts in normal human tissues. However, there is no clarity about the role of TIC in carcinogenesis. Hybrid proteins resulting from chimeric genes regarded as ideal markers which are specific for disease entities can be potential targets for the treatment due to their key roles in malignant transformation. In some tumors fusion genes may play primary role, and in the others may represent an additional mechanism during subclonal selection. The aim is to briefly review and discuss the occurrence and biologic relevance of chimeric genes in hematologic malignant diseases, sarcomas and epithelial neoplasms.