PURPOSE: Single motherhood is associated with increased psychosocial risks, affecting both mothers and their minor children. However, little is known about the specific psychosocial impact of maternal cancer in single mothers (SMs). This study compared psychological burden, quality of life, specific problems, and parental concerns between SMs and partnered mothers (PMs) affected by cancer and caring for minor children. METHODS: Cross-sectional analysis of baseline data from a multicenter, non-randomized, controlled trial in Germany (Family-SCOUT). SMs and PMs affected by cancer were assessed for psychological burden (anxiety, depression, distress), quality of life, practical, family, emotional, spiritual/religious, and physical problems and parental concerns. RESULTS: A total of 54 SMs and 245 PMs were included. SMs reported more practical problems (p = 0.008, d = 0.44) and parental concerns than PMs (p = 0.011, d = 0.40). After controlling for demographic and clinical group differences, practical problems (p = 0.009, OR = 1.53) and parental concerns (p = 0.015, OR = 1.73) remained significantly associated with single motherhood. SMs and PMs did not differ in anxiety, depression, distress or quality of life. Overall, a large proportion of mothers reported clinically relevant elevated levels of anxiety (71.9%), depression (46.8%) and heightened distress (82.3%). CONCLUSION: In this sample, the psychological burden of mothers with cancer who care for minor children did not differ based on whether they were parenting alone or together with a co-parent. However, SMs reported more practical problems and parental concerns than PMs, emphasizing the need for targeted support in practical problem-solving and child care for SMs. TRIAL REGISTRATION NUMBER: NCT04186923, 5. December 2019.