Abstract: Anal sac adenocarcinoma (ASA) is an aggressive tumor from the epithelium of anal sac gland. Clinico-genomics data of 121 dogs with ASA from FidoCure® Precision medicine platform were evaluated. Eighty-six dogs had genetic alterations such as somatic mutations, BRCA1/2 somatic/germline deleterious mutations or CNVs. KMT2D (16/121), BRCA2 (13/121), PARP1 (11/121) and BRCA1 (10/121) were the most common alterations identified. Six dogs had an ERBB2 mutation: 5 located at position K676E and one at position V659E. The ERBB2 K676E mutation has been identified solely in ASA across 2811 canine tumors. Targeted therapies were recommended based on detected mutations. Overall survival of dogs with local lymph node involvement receiving targeted therapy (TT) and chemotherapy (CHEMO) was 794 days (n: 24), for dogs treated with TT only 462 days (n: 11), and 934 days (n: 6) for dogs receiving TT+CHEMO and radiation therapy (p= 0.0124). Survival of dogs with no lymph node involvement treated with TT only were 1211 days (n: 11) and 1186 days (n: 5) for TT+CHEMO (p=0.8399). Survival of dogs with lymph node involvement receiving TT only recommended based on genomic targets was 721 days (n: 5) compared to 462 days (n: 6) when TT was used alone regardless of the genomic profile (p=0.9927). This is the first time ERBB2 K676E was exclusively identified in dogs with ASA. More studies are needed to identify opportunities to use TT guided by genomics to improve survival of dogs with ASA.