Lipid composition of atherosclerotic plaques is considered to be one of the primary indicators of plaque vulnerability. Therefore, a specific diagnostic or imaging modality that can sensitively evaluate plaques’ necrotic core is highly desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information from an arterial wall with great optical contrast and long acoustic penetration depth. Within the near-infrared window, a 1210-𝑛𝑚 optical source is usually chosen for IVPA applications as lipids exhibit a strong absorption peak at that wavelength due to the second overtone of the C-H bond vibration within the lipid molecules. However, other arterial tissues also show some degree of absorption near 1210 𝑛𝑚 and thus generate undesirably interfering PA signals. In this study, a theory of the novel Frequency-Domain Differential Photoacoustic Radar (DPAR) modality is introduced as an interference-free detection technique for accurate and reliable evaluation of vulnerable plaques. By assuming two low-power continuous-wave (CW) optical sources at ~ 1210 𝑛𝑚 and ~ 970 𝑛𝑚 in a differential manner, DPAR theory and the corresponding simulation study suggest a unique imaging modality that can efficiently suppress any undesirable absorptions and system noise, while dramatically improving PA sensitivity and specificity toward cholesterol contents of atherosclerotic plaques.