Some pathology tests that involve immunohistochemistry (IHC) staining now have in situ hybridization (ISH – including chromogenic ISH [CISH] and fluorescence ISH [FISH])) technology being used either as alternative or confirmatory methods. This technical note, based on a critical appraisal, shares opinion on ISH and IHC discrepancy resolution as well as adoptability of the ISH methods by pathology services in low-mid income countries. The report that is appraised involved 174 cases of human epidermal growth factor receptor 2 (HER2) from pathology archives. The CISH, FISH, and IHC slides were reviewed by two pathologists and consensus scores assigned if a discrepancy occurred. The report indicated absolute concordance between the CISH and FISH results, with 82% between IHC and ISH. No equivocal case was reported. The report was assessed to resolve the 18% discrepancy between the IHC and ISH results that were otherwise unequivocal. Recent guidelines for Her2 testing, jointly issued by the American Society of Clinical Oncology and the College of American Pathologists, is still being debated – for example, the associated workload implications and challenges for support in most health care systems. What is being contributed to the discourse is that using ISH to confirm positive IHC is not recommended and could create discrepancies that are, as yet, difficult to resolve. The cost of performing ISH is something to consider, especially in low-mid income countries where affordability and availability of tests are abysmal. CISH, which speculated to be a less expensive alternative to FISH, should be given serious consideration.