The tumour suppressor gene, TP 53 (commonly also called p53) has multiple, important cellular functions involving control of apoptosis, downstream cell cycle regulation via p21 and cyclin dependent kinases, and control of tumour angiogenesis. Somatic mutation of TP 53 is considered to be the most common genetic mutation in human cancer. Mutations of the gene are associated with drug resistance and poor patient prognosis in human cancers. Immunohistochemistry to detect mutated TP 53 is unreliable and molecular biology approaches are therefore preferable for its assessment. This chapter describes protocols for the 'gold standard', but perhaps complex and time consuming, methods for sequencing TP 53, by cDNA and genomic based sequencing techniques.