tRNA fragments (tRNA derived fragments or tRFs) are small single stranded RNA molecules derived from pre-tRNAs and mature tRNAs. tRFs have been known for a number of years, but previously they were believed to be not important products of tRNA degradation. tRFs can be unique, like tRF-1 s, or redundant, like tRF-3 s and tRF-5 s. Scientific interest in tRFs has drastically increased in the last 5 years. Many studies have found that tRFs are differentially expressed in many normal cellular processes as well as in transformed cancer cells. Dysregulation of tRFs expression have been reported in multiple major types of cancer including solid cancers and lymphoid malignancies. However the exact molecular role of these molecules is not entirely clear. A number of studies proposed that tRFs can work as microRNAs by targeting gene expression. Here we discuss recent studies showing differential expression of tRFs in many cancers as well as what is currently known about tRFs biological functions in cancer cells.