CONTEXT: Several instruments have been developed to assess the symptom burden and fatigue produced by cancer and its treatment. However, little research has been conducted in Latin American Spanish-speaking patients. OBJECTIVES: The aim of the study was to assess the psychometric properties of the Spanish versions of two commonly used patient-reported outcome measures, the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), and the fatigue subscale of the Functional Assessment of Cancer Therapy-General (FACT-G), the FACIT-Fatigue. METHODS: A classic psychometric approach was followed to assess the reliability and validity of the instruments. Responsiveness to change and effect sizes were calculated. RESULTS: The translated version of the MSAS-SF proved to be comprehensible and easy to complete. Cronbach alpha reliability coefficients ranged from acceptable to excellent for the MSAS-SF subscale scores and the FACIT-Fatigue. There was evidence of convergent validity between the physical and the psychological subscales of the instruments. The MSAS-SF could discriminate among the known groups according to Eastern Cooperative Oncology performance status and level of anemia, and showed responsiveness to change of symptom burden at two times of treatment. CONCLUSION: The study showed that both the MSAS-SF and the FACIT-Fatigue have good reliability and validity for use with patients with cancer in Uruguay. When used simultaneously, these instruments may provide a complete picture of the impact of cancer and its treatment on the patient's quality of life.