A high‐density 384‐lane microfabricated capillary array electrophoresis device is evaluated for high‐throughput single‐strand conformation polymorphism (SSCP) analysis. A delayed back bias direct electrokinetic injection scheme is used to provide better than 10‐bp resolution with an 8.0‐cm effective separation length. Separation of a HaeIII digest of ΦX174 yielded theoretical plate numbers of 4.0×10⁶. Using 5% PDMA containing 10% glycerol and 15% urea, 21 single‐nucleotide polymorphisms (SNPs) from HFE, MYL2, MYL3, and MYH7 genes associated with hereditary hemochromatosis (HHC) and hereditary hypertrophic cardiomyopathy (HCM) are discriminated at two running temperatures (25°C and 40°C), providing 100% sensitivity. The data in this study demonstrate that the 384‐lane µCAE device provides the resolution and detection sensitivity required for SSCP analysis, showing its potential for ultrahigh‐throughput mutation detection.