The zebrafish system has been established as a useful model for the study of carcinogenesis. The cytogenetic characterization of the genome is vital for furthering our understanding of the progression of the disease. Establishing a basic description of the zebrafish chromosomal karyotype and markers for each specific chromosome permitted the first cytogenetic characterization of the reference genome and the genome of cancer models. As the field of cancer cytogenetics is highly dependent on technology, each advance in technique and methodology has resulted in a corresponding wave of discoveries. We have witnessed great improvement in the resolution of the assays allowing for more detailed characterization of cytogenetic abnormalities, including the efficient and accurate identification of DNA copy number alterations of specific chromosomal regions. Herein, we will discuss major advancements in the field of cytogenetics, along with examples of how these technologies have been utilized in studies to characterize zebrafish cancer disease models. Finally, we will discuss the current state of the field and how microarray technology are being implemented to scan the whole genome at high resolution for DNA copy number alterations observed in various cancer types throughout the progression of the disease.