Chromosomal translocations are very common in human cancer. The molecular mechanisms of chromosomal translocations are complex and are not fully understood. Recent studies showed organization of genomes is higher-order in the nucleus and every chromosome or chromatin has its preferential position and territory. These findings suggest the spatial arrangements of chromosomes and gene loci in the interphase nucleus are responsible for non-random chromosomal translocations in human cancer. Chromosomal translocations are favored in neighboring chromosomes or genes in spatial proximity within the nucleus. Chromosomal translocations leading to cancer are generally via two ways, formation of oncogenic fusion protein or oncogene activation by a new promoter or enhancer. This review focuses mainly on the recent advances in oncogenic chromosomal translocations in human cancer.