Patients with primary biliary cirrhosis (PBC) generate a variety of autoantibodies, which are primarily directed against mitochondrial antigens (AMA). However, a subgroup of patient sera are also positive for antibodies to nuclear components (ANAs). At indirect immunofluorescence (IIF), PBC sera mostly produce homogeneous, nuclear dot, speckled, centromere, or rim-like patterns. During the last two decades, a number of nuclear structures have been recognized as specific targets of ANA in PBC. These include Sp100 and promyelocytic leukemia proteins, which generate a nuclear dot IIF pattern, and two components of the nuclear pore complex specifically associated with a perinuclear pattern (i.e., gp210 and p62). In recent years, the clinical significance of ANA in PBC has been widely investigated and data indicate that, unlike AMAs, PBC-specific ANAs correlate with disease severity and may therefore be a marker of poor prognosis.