Tumor profiling assay workflows start from a tissue biopsy sample that is formalin fixed and paraffin embedded (FFPE), a process that introduces various kinds of damage in the nucleic acids in the tissue specimen. Reference materials that closely mimic the damage profile of patient FFPE samples are lacking. Depurination, depyrimidination, deamination, oxidation, nicks, and double strand breaks may be found in DNA extracted from FFPE tissue, despite the use of extraction kits that attempt to repair some of this damage. We have developed a formalin-damaged, multiplexed biosynthetic reference material, Seraseq® Compromised FFPE Tumor DNA, as well as a companion wild-type (WT) material, Seraseq Compromised FFPE WT, to mimic the damage found in patient samples that can be used to assess the entire tumor profiling workflow. We compared the performance of these reference materials in downstream assays to that of FFPE material with minimal DNA damage such as the Seraseq FFPE WT (DNA/RNA) RM product.