Correct classification of nonalcoholic steatohepatitis (NASH) liver biopsies is of critical importance and relies on correct orientation to microscopic liver architecture. Centrizonal arteries can cause central zones to be mistaken for portal tracts, especially in the setting of centrizonal ductular reaction, and result in either missed diagnosis or inaccurate staging of NASH. A total of 100 randomly selected biopsies from NASH Clinical Research Network participants (February 2005 to August 2006, fibrosis stage >1a) were evaluated for arteries and CD34-positive microvessels in the centrizonal region. Prevalence of both centrizonal arteries and CD34-positive microvessels was graded as 0 (none in central zones), 1 (1 to 2 central zones with vessels), 2 (<50% of central zones with vessels), or 3 (≥50% of central zones with vessels). Centrizonal arteries and CD34-positive microvessels were present in 40 and 100 cases (40% and 100%), respectively. Arteries and CD34-positive microvessels were more commonly found in central zones in biopsies with greater degrees of fibrosis (62% with arteries in stage 3 to 4 versus 21% in stage 1 to 2 and 70% with microvessels in stage 3 to 4 versus 25% in stage 1 to 2), with increased prevalence of both centrizonal arteries and CD34-positive microvessels correlating directly with fibrosis stage (P<0.001). Ductular reaction was a common finding (55%) in patients with central zone arteries. The presence of centrizonal arteries must be recognized to allow for correct orientation to liver architecture in NASH and, together with the finding of increased CD34-positive microvessel formation in higher-stage fibrosis, suggests a possible association between neoangiogenesis and NASH progression to cirrhosis.