It is well known that several chromosomal syndromes as well as chromosomal instability syndromes are cancer prone. A thorough cytogenetic study (in certain cancer prone syndrome) that may bring out any associated factors if any in the transformation of precancerous status to cancerous status making use of both chromosomal aberrations (CA) analysis and cytokinesis block micronucleus cytome assay (CBMN cyt) was undertaken. Blood samples were collected from the cancer prone chromosomal syndromes- Down syndrome (n=20); Gonadal Dysgenesis (n=5); Chromosomal instability syndromes - Aplastic Anemia (n=5).Age and sex matched ethnic controls (n=30). A significantly higher frequencies of CA, micronuclei (MNi) and various nuclear anomalies were observed in the patients in comparison to the controls (p<0.001). The Aplastic Anemia patients showed a higher frequency of genomic instability followed by Gonadal Dysgenesis and Down syndrome. Therefore these biomarkers could be used to predict the risk of malignant transformation of cancer prone chromosomal syndromes.