Major efforts are underway to systematically define the somatic and germline genetic variations causally associated with disease. Genome‐wide genetic analysis of actual clinical samples is, however, limited by the paucity of genomic DNA available. Here we have tested the fidelity and genome representation of ϕ29 polymerase‐based genome amplification (ϕ29MDA) using direct sequencing and high density oligonucleotide arrays probing >10 000 SNP alleles. Genome representation was comprehensive and estimated to be 99.82% complete, although six regions encompassing a maximum of 5.62 Mb failed to amplify. There was no degradation in the accuracy of SNP genotyping and, in direct sequencing experiments sampling 500 000 bp, the estimated error rate (9.5 × 10^–6) was the same as in paired unamplified samples. The detection of cancer‐associated loss of heterozygosity and copy number changes, including homozygous deletion and gene amplification, were similarly robust. These results suggest that ϕ29MDA yields high fidelity, near‐complete genome representation suitable for high resolution genetic analysis.