Chromosomal rearrangements resulting in the formation of fusion genes are common events in carcinogenesis. More than 440 fusion genes found in both malignant and benign tumors are known. The mechanism of transcription-induced chimerism (TIC) contributes to the fusion transcripts found in normal human tissues. However, there is no clarity about the role of TIC in carcinogenesis. Hybrid proteins resulting from chimeric genes, which are regarded as ideal markers specific for disease entities, can be potential targets for the treatment owing to their key roles in malignant transformation. Fusion genes may play a primary role in some tumors and they may represent an additional mechanism acting during subclonal selection in other tumors. The review considers in brief and discusses the occurrence and biologic relevance of chimeric genes in hematological malignant diseases, sarcomas, and epithelial neoplasias.