We present a microfluidic ‘megapixel’ digital PCRdevice that uses surface tension–based sample partitioning and dehydration control to enable high-fidelity single DNAmolecule amplification in 1,000,000 reactors of picoliter volume with densities up to 440,000 reactors cm−2. This device achieves a dynamic range of 107, single-nucleotide-variant detection below one copy per 100,000 wild-type sequences and the discrimination of a 1% difference in chromosome copy number.