OBJECTIVE Primary liver cancer (PLC) presenting as pyogenic liver abscess (PLA) is potentially life-threatening, but has been occasionally reported, especially for cholangiocarcinoma. METHODS Medical records of nine patients who presented as PLA, but were eventually confirmed as hepatocellular carcinoma (HCC; n = 5) or intrahepatic cholangiocarcinoma (IHCC; n = 4), from September 1997 through April 2011, were retrospectively reviewed. RESULTS Presenting symptoms included fever, chills, right-upper-quadrant abdominal pain, nausea, vomiting, weight loss, and diarrhea. Physical signs included tenderness in the right-upper-quadrant abdomen, jaundice, and ascites. With the exception of elevated alpha-fetoprotein (AFP) in HCC patients and elevated carbohydrate antigen 19-9 (CA19-9) in IHCC patients, lab results were not significantly different between these nine patients and PLA patients. All the nine patients underwent invasive treatment in addition to antibiotics. CONCLUSIONS Elevated AFP and CA19-9 could suggest HCC and IHCC in patients with symptoms/signs typical of PLA. Contrast-enhanced computed tomography could be helpful in patients with normal AFP and CA19-9. Making an accurate and early diagnosis and seizing the opportunity of surgery are essential to improve the management strategies of patients with PLC mimicking PLA.