Objective: This review aims to discuss the clinical application of cytogenetic and molecular testing in the diagnosis and prognosis of orbital tumors and, in so doing, highlight the basis of these methods, their advantages, and limitations. Summary: Specific chromosomal aberrations are detected in many lymphoproliferative neoplasms, soft tissue tumors, and in a few benign tumors of the orbit. Detection of these characteristic chromosomal translocations is most helpful to refine the diagnosis and classification, especially when the tumor is poorly differentiated and shows overlapping morphological features with another tumor type. This review outlines orbital tumors with characteristic chromosomal translocations and the relative frequency of detecting the genetic mutation. Various genetic techniques are available for genetic testing, including karyotyping, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and genomic polymerase chain reaction (PCR). As yet, the newer methods of array-comparative genomic hybridization (array-CGH) and expression profiling are most commonly used in research settings or in large specialist centers, and their general application to cancer diagnostics is limited by their cost. Therefore, this review focuses on the methodologies that should be available to most diagnostic units. It is true that “one size does not fit all” in this field and that a combination of molecular techniques may be needed to confirm results at the genomic and transcriptional levels.