UNLABELLED: The chromosomal characterization of nasopharyngeal angiofibroma (NPF) of Indian origin seems important as it is consistently absent in literature. Routine karyotyping (G-banding) and fluorescence in situ hybridization (FISH) analysis was undertaken using CMYC, TP53 CEPX/Y probes in 9 cases of NPF wherein chromosomal characteristics were correlated with clinical parameters. Karyotype profile of venous sample from every case was normal. Following FISH analysis, 5 (55%) cases showed deleted CMYC allele while 4 (44%) showed deleted TP53. In addition, loss of Y centromere was evident in 1 case. Despite definite trends, no significant correlation with clinical parameters and FISH expression/ G-banding karyotyping could be appreciated. The peripheral blood karyotype cannot predict any significant parallel picture in solid tumour. Solid tumour karyotyping and FISH have a definite potential to screen the genetic abnormalities. While high cost of FISH probes and the required expertise may limit its routine clinical use, this technique can be combined with other molecular tools for better results. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12070-024-05171-z.