Antibodies have proven to be effective in immunohistochemistry for the diagnosis of tumours and for the detection of cell surface markers prior to commencement of immunotherapy. However, batch-to-batch variation and cross-reactivity can limit their effectiveness. Chemical antibodies, also known as aptamers, are small pieces of DNA or RNA that are generated in a similar manner to antibodies – incubation with the target protein – and bind in exactly the same manner as antibodies via the ‘lock and key’ mechanism. Aptamers show very high specificity to their target and, as they are chemically synthesised, they can be easily derivatised with detection moieties at one or many pre-specified locations along their sequence, depending on the application. Having generated an aptamer targeting EpCAM, we tested its sensitivity in number of invasive ductal carcinoma cases using a chromogenic staining system, and showed that aptamers directed against EpCAM demonstrated superior sensitivity in paraffin embedded tissues. In a number of cases, conventional monoclonal antibodies failed to detect low levels of EpCAM in the breast tumour or the lymph node. This aptamer showed no non-specific staining or cross-reactivity and displayed a much more robust detection of EpCAM. Notably, sensitive staining was achieved in less than 15 minutes. From a clinic-pathological point of view, this has both prognostic and therapeutic significance, the latter due to the potential for immunotherapy trials. Results from EpCAM immunotherapy trials has been mixed, as there is currently no EpCAM antibody that is robust enough to be able to detect EpCAM expression in all pathological tissues. Therefore, the results from this study have important clinical significance for breast cancer diagnosis and suggest that aptamers have a promising future in the diagnostic laboratory.