Small non-coding microRNA (miRNA) molecules are 19- to 24-nucleotide RNA molecules that regulate post-transcriptional gene expression. Chromosome alterations, including genome deletions, point mutations, and amplifications, may determine whether miRNAs behave as tumor suppressor genes or oncogenes in human cancers. MiRNA profiling has become a successful tool for characterizing diversified solid tumors. This review will discuss the general mechanism of miRNA function and how their function is affected by cytogenetic alterations. Genomic regions that are frequently deleted or amplified in cancer often code for miRNA. A PubMed database search for expression studies linking miRNA genes with cancer development revealed clusters of as few as three miRNAs that had been previously associated with cancer in several expression studies. The genomic locations most frequently associated with miRNA:cancer "interactions" were distributed among all chromosomes but more often among seven separate chromosomes (some with two locations per chromosome). Some of the miRNAs were associated with up to 12 different human cancers. According to the chromosomal locations of the miRNA genes, some chromosome locations are more often associated with cancer development and its progression. In conclusion, miRNAs likely work in concert with other genes to contribute to the development and progression of complex diseases such as cancer.