Over the past five decades, a plethora of nonrandom chromosomal abnormalities have been consistently reported in malignant cells facilitating the identification of cancer-associated protein coding oncogenes and tumor suppressors. The genetic dissection of hot spots for chromosomal abnormalities in the age of the sequenced human genome resulted in the discovery that microRNA (miRNA) genes, encoding for a class of small noncoding RNAs, frequently resides in such genomic regions. The combination of nonrandom chromosomal abnormalities and other types of genetic alterations or epigenetic events contribute to downregulation or overexpression of miRNAs. The consequent abnormal expression of miRNAs affect cell cycle, survival and differentiation programs and selective targeting of these noncoding genes could provide novel therapeutic options for killing the malignant cells.