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Misinterpretation of non-content-based invalid (e.g., random, fixed) responding as overreporting or underreporting is likely to adversely impact test interpretation and could bias inferences about examinee intentions. We examined the impact of non-content-based invalid responding on the following Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) content-based invalid responding indicators: Infrequent Responses (F-r), Infrequent Psychopathology Responses (FP-r), Infrequent Somatic Responses (FS), Symptom Validity (FBS-r), Response Bias Scale (RBS), Uncommon Virtues (L-r), and Adjustment Validity (K-r). In 4 samples from which invalid responders were excluded, we systematically inserted increasing percentages of random, acquiescent, or counter-acquiescent item responses ranging from 0% to 100% and examined the impact that non-content-based invalid response styles had on the content-based invalid responding indicators. F-r, FP-r, FS, RBS, and L-r were susceptible to non-content-based invalid responding, whereas FBS-r and K-r were unaffected. Individuals with Variable Response Inconsistency (VRIN-r) and True Response Inconsistency (TRIN-r) elevations were removed, and the frequencies of content-based invalid responding elevations were then reexamined for false indications of feigning. Findings were consistent across samples and emphasize the need to screen for non-content-based invalid responding before screening for content-based invalid responding in the assessment of personality and psychopathology. VRIN-r and TRIN-r were useful in detecting most—but not all—cases of non-content-based invalid responding. A small but meaningful percentage of the remaining individuals were misclassified as overreporters (i.e., false feigners) by FP-r and FS. Clinicians should interpret FP-r and FS with some caution in the presence of moderate levels of non-content-based invalid responding. Post hoc examinations of scale characteristics indicated that the most susceptible scales were brief, consisted of rarely endorsed items, included a relatively high percentage of true-keyed items, and required a low percentage of endorsed items to reach clinical significance.