Currently, there are no recommended alternative assays for HER2 cases deemed equivocal by immunohistochemistry and fluorescent in situ hybridization. Digital PCR (ddPCR), a highly accurate method to determine DNA copy number, could be a robust alternative for clinical HER2 diagnostics. HER2 and CEP17 copy numbers were quantified using two ddPCR platforms (QX200 and RainDrop) in 102 samples of invasive breast cancers. Compared to routine assays, ddPCR gave a sensitivity and specificity of 82.8% and 97.3% respectively, with a kappa value of 0.833 (p < 0.001). Moreover, the method proved to be robust as the results from two platforms was highly correlated (R2 = 0.91; Concordance rate = 97%; κ = 0.923, P < 0.001). Its performance was further tested on 114 HER2 equivocal cases in an independent validation cohort. 75% (21/28) of cases with HER2 amplification and 95% (82/86) of HER2 non-amplified case were classified as positive and negative by ddPCR respectively (κ = 0.709, P < 0.001). Notably, in the HER2 amplified cases, a lower percentage of HER2 positive cells could be related to the discordant results. Altogether, ddPCR is a robust alternative for clinical HER2 diagnostics. However, intratumoral heterogeneity of HER2 status still pose a challenge for HER2 analysis by ddPCR.