Introduction/Objective IHC staining for biomarkers ER, PR and HER-2 (CerB2) forms an essential component of breast cancer management and prognostication. Staining for these biomarkers is dependent on optimal fixation of the specimen in formalin. Scoring systems employed for ER and PR grade the intensity of the nuclear staining along with the percentage of the cells stained. This study aims to determine if ultrasound gel used during core biopsy as opposed to water affects immunohistochemical staining of biomarkers ER and PR in breast cancer specimens, following an observation that ultrasound gel assisted core biopsies may affect ER/PR nuclear staining scores through excess cytoplasmic staining. Methods/Case Report We included a total of 50 cases of invasive breast carcinoma diagnosed on core biopsy from KK Women’s and Children’s Hospital from February 2019 to July 2020. These included 25 cases with gel and 25 cases with water applied to the breast prior to the procedure. All biopsies were optimally fixed in formalin as per recommended latest ASCO/CAP guidelines. The control group included 25 resection cases of invasive breast carcinoma which had neither gel nor water and had been optimally fixed in formalin. Cytoplasmic staining for ER and PR was graded as being present or absent and was compared against the excision specimens (control group) to determine if using the gel was significant in producing cytoplasmic staining. The data was analyzed on SPSS using multiple logistic regression. Results (if a Case Study enter NA) Using the gel appeared to be statistically significant in producing cytoplasmic staining for ER (p=0.042) as opposed to using water (p=0.274). For PR staining, both gel-based (p=0.250) and water-based media (p=0.286) were not statistically significant in causing cytoplasmic staining. Conclusion The preliminary findings of this small retrospective case-control study gives an insight that gel-based media may have a role in causing cytoplasmic staining for oestrogen receptor in breast cancer biopsy specimens which may interfere with accurate scoring and impact results of external quality assurance schemes to which laboratories subscribe to. However the study is limited by the small sample size and exclusion of any other pre- analytical factors like needle bore or number of cores taken which may have had an impact on the staining.