Purpose: Breast carcinomas express the Na+/I− symporter and may—albeit not a routine procedure—be imaged with 123iodide (123I) and 99mtechnetium-pertechnetate (99mTcO4
−) scintigraphy. The aim of our prospective study was the comparison of 99mTcO4
− -and 123I-single-photon emission computed tomography (SPECT) with 18F-2-fluoro-2-deoxy-D-glucose–positron emission tomography (FDG-PET) in patients suspicious for breast cancer. Methods: Twenty-nine (29) untreated patients suspected of having breast carcinoma were prospectively examined with thorax SPECT with 99mTcO4
− (n = 19) or 123I (n = 10), respectively, and FDG-PET (n = 29) prior to biopsy. Tumor-to-background ratios (TBRs) were calculated for SPECT findings. Mean and maximum standardized uptake values (SUVs) were calculated for PET findings. Findings were compared in an intra-individual lesion-to-lesion analysis. Results: In 28 of 29 patients, malignancy was verified with histopathology. In imaging the primary tumor, sensitivities of 99mTcO4
−-SPECT, 123I-SPECT, and FDG-PET were 63%, 67%, and 89%, respectively. TBR maximum was 2.6 ± 1.1 in 99mTcO4
−-SPECT and 2.3 ± 0.6 in 123I-SPECT. In FDG-PET, mean tumor SUV was 4.1 ± 4 and maximum tumor SUV was 5.4 ± 5.1. In contrast to FDG-PET, 99mTcO4
−-SPECT was ineffective in imaging nodal and distant metastases in the thorax, and 123I-SPECT failed in imaging lymph node infiltrations. Distant metastases were not present in patients of the 123I group, and the value of 123I-SPECT was not evaluated. Conclusions: In contrast to FDG-PET, 99mTcO4
− and 123I-SPECT are ineffective in imaging breast carcinoma in clinical practice.