Detection of mutations is of central importance in the study of genetic and malignant diseases. Mutation detection helps us in understanding the protein structure, function, and expression. More than that, it is also important for presymptomatic/antenatal diagnosis, confirmation of the genetic cause of the disease and the mode of inheritance of a disease in a particular family, the prediction of clinical phenotype, and the potential for diagnostic analysis in the case of families with incomplete pedigrees or with new mutations. Therefore, the importance of direct mutation analysis cannot be understated. Breast cancer is one of the most common malignancies affecting women worldwide. Genetic predisposition for familial early onset of breast cancer accounts for approximately 5–10% of all breast cancers. Mutations in two autosomal dominant genes, BRCA1 and BRCA2, have been linked to familial breast cancer (1–4). Mutations in these two genes were predicted to account for 85–90% of hereditary breast and ovarian cancer cases. Genetic screening might contribute to cancer control by identifying a group of at-risk patients who could benefit from augmented screening or prophylactic measures that accompany genetic susceptibility testing for cancer. Several techniques are available for detecting mutations in BRCA1. This chapter describes a relatively new technique of conformation sensitive gel electrophoresis (CSGE). A rapidly increasing number of methods is available for detection of mutations. Choosing a mutation detection method requires careful consideration of many factors. The tests must be easy to use and cost-effective. Accuracy in the 99.9% range and dayto-day reliability are the basic requirements for the acceptance of new technologies, but attributes such as cost and convenience are also important. The general strategy adopted for detecting mutations is to amplify the gene in small fragments, analyze the fragments by a rapid technique and then sequence only those fragments positive for mutation by a rapid technique to locate and identify the nature of mutation. The very commonly used rapid techniques are single-stranded conformation polymorphism (SSCP) (5), enzymatic or chemical cleavage of mismatched base pair (6–12), and differential unfolding of homoduplexes and heteroduplexes by denaturing