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This study presents a systematic defect diagnosis to identify 'culprit physical features' that are potentially responsible for yield loss. A 'single location in‐a‐cluster' technique is proposed to diagnose multiple defects that may not be diagnosed by traditional 'single location at‐a‐time' technique. A statistics technique, 'analysis of variance', is conducted to reduce noise from random defects. Simulations on five ISCAS'89 circuit demonstrate the effectiveness of the authors' techniques. An experiment on an industrial design manufactured in 55 nm technology discovered a suspected culprit physical feature. [ABSTRACT FROM AUTHOR]