Amyloid refers to a family of abnormal proteins that share a common fibrillar β-pleated sheet structure that gives it unique optical and staining properties. In addition to the fibrillar component, amyloid deposits contain a universal amyloid P component. Detection of amyloid in myocardial tissue with Congo red alone is difficult and tedious. We evaluated amyloid P immunohistochemical (IHC) staining in cardiac biopsies and compared them to Congo red interpretation, which is the gold standard for detecting amyloid. IHC for amyloid P expression (monoclonal antibody clone 6E6 1/200) was performed on 45 myocardial tissues. Congo red staining results were obtained from pathology reports or newly stained Congo red slides. Homogenous 2-3+ amyloid P staining in greater than 10% of muscle fibers was considered positive; fibrillary amyloid P staining in less than 10% of muscle fibers was considered negative. Congo red salmon-colored stain with apple-green birefringence was interpreted as positive. Of the 45 cases, amyloid P was positive in 26/45 (58%) and negative in 19/45 (42%). Congo red was positive in 25/45 (56%) and was negative in 20/45 (44%). The one discordant case was amyloid P positive, Congo red negative, and positive by thioflavin T and electron microscopy. Results by amyloid P IHC and Congo red are similar (P = 1.00). Amyloid P has a sensitivity of 100% and specificity of 95%. Amyloid P immunostain for cardiac amyloid is sensitive and specific. Interpretation in most cases is easier than with the gold standard Congo red staining and apple-green birefringence. We recommend routine use of amyloid P IHC, in addition to H&E and Congo red stains. In equivocal cases, electron microscopy may be useful.