Background: Diagnosis of cancer in one’s child causes not only social but also psychological devastation for the whole family especially mothers. Depressed mothers are less able to help their sick child cope with intensive treatments. This study was done to identify frequency and severity levels of depression in mothers of children with cancer. Methods: Across sectional study was conducted from September 2011-March 2012 at Aga Khan University Hospital, pediatric oncology clinics. Hundred mothers were enrolled according to inclusion and exclusion criteria. A pre-coded validated questionnaire regarding mothers and child’s demographics along with Hamilton-D (HAM-D), a depression screening and severity scale, was used. Data was analyzed using SPSS (19.0), frequencies, and proportions were reported accordingly.Results: Forty-three percent mothers were in the age group of 30-39 years. Seventy-eight percent mothers were found to be depressed. Out of those 69% had mild, 25% moderate, 5% severe, and 1% had very severe depression.Conclusion: Majority of mothers were found to be depressed in this study. This known high level of depression in mothers, it is recommended that early non-therapeutic and/or therapeutic interventions should be done to help them cope with their situation.