The present study focus on optical sensing of breast cancer antigen 15.3 (CA 15.3) using cadmium sulphide quantum dot (CdS-QD) in saline and serum samples spiked with antigen. The surface of CdS-QD was modified by cysteamine capping followed by tagging of CA 15.3 antibody. The samples were characterised using UV-visible absorption spectroscopy (UV-VIS Spectroscopy), Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HRTEM) attached with energy-dispersive X-ray spectroscopy, phase contrast inverted epi-fluorescence microscopy and photoluminescence (PL) spectrophotometry (EDS). The CdS-QD showed a mean diameter of 3.02 ± 0.6 nm. The complex formed after antigen-antibody interaction resulted in distinguishable optical and fluorescence intensity with respect to varying concentration of antigen. The PL study revealed that CA 15.3 antibody labelled CdS QD can detect CA 15.3 tumour marker even at very low concentration of 0.002 KU/L with a constant response time of 15 min. This study clearly indicates that detection of CA 15.3 at low concentration is possible using surface modified CdS QD in serum samples and can find immense applications in biosensor development for detection of breast cancer marker similar to various automated detection kits available in market.