One of the main challenges in HER2 testing is the variability in interpretation of IHC results. The scoring system ranges from 0 to 3+, with scores of 0 and 1+ considered negative, 2+ as equivocal, and 3+ as positive. Equivocal cases often require additional testing with FISH for a definitive diagnosis. Another challenge is the heterogeneity of HER2 expression within different areas of the same tumor or between primary and metastatic sites.