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Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3–31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2–16 years later show that many primary DCIS had already undergone whole-genome doubling and clonal diversification and that they shared genomic lineages with persistent subclones in the recurrences. Evolutionary analysis suggests that most DCIS cases in our cohort underwent an evolutionary bottleneck, and further identified chromosome aberrations in the persistent subclones that were associated with recurrence. [Display omitted] • Arc-well is a high-throughput single-cell DNA-seq method for archival FFPE tissues • Arc-well reliably profiled thousands of cells from 27 FFPE tissues archived for years • Persistent subclones from DCIS and matched recurrences were identified • Most DCIS cases in this cohort underwent an evolutionary bottleneck Arc-well enables reliable high-throughput single-cell genomic sequencing from formalin-fixed paraffin-embedded clinical oncology samples archived for years to decades, and the application of this method reveals genomic features and evolutionary models in ductal carcinoma in situ associated with cancer progression and recurrence. [ABSTRACT FROM AUTHOR]