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Background: Psychological distress is widespread in cancer patients as it is considered one of the traumatic events which significantly affect the quality of life of cancer patients.: To compare psychological disorders between cancer patients and a control group regarding the prevalence of associated mental health disorders and the level of positive and negative affect. The study also examines the association of affective states with mental health disorders. Methods: This case-control study comprised 400 participants; 200 cancer cases attending Minia Oncology Center age and sex-matched with 200 community-based controls during the period from November 2021 till November 2022. Results: As regards psychiatric disorders, moderate to severe depression, anxiety, and stress are significantly higher among cases (69%, 68%, and 52.5%) compared to controls (31%, 32%, and 47.5%) respectively. The overall negative affect mean score is significantly higher among cases (25.88±6.54) compared to the control group (19.74±1.78). There are significant positive correlations of the negative affect score with psychological disorders scores with stronger associations among cases compared to controls. Conclusion: Psychological disorders are more prevalent among cancer cases compared to the controls with significant associations of affective states with mental health disorders. Recommendation: Integrating psychological screening is recommended for cancer patients as a routine in cancer care and referral to a mental health professional for tailoring psychological counseling and supportive care services to meet their needs.