Background Pittsburgh compound B ([11C]‐PIB) identifies amyloid‐β (Aβ) deposition in vivo. Asymptomatic Aβ deposition has been reported consistently in some healthy older subjects. Of patients with frontotemporal dementia, those who have later onset have a higher potential for Aβ deposition. Objective Comparison of Aβ deposition in Alzheimer's disease (AD), healthy older controls, and patients with early‐ and late‐onset semantic dementia (SD), a subtype of frontotemporal dementia. Methods Subjects were recruited from tertiary academic care centers specializing in assessment and management of patients with neurodegenerative disease. We used the radiotracer [11C]‐PIB in a high‐resolution positron emission tomography scanner to evaluate 11 participants with SD (six with onset before age 65 and five with later onset), 9 with probable AD, and 10 controls over age 60. The main outcome measures were frontal, temporal, parietal, and total [11C]‐PIB standardized uptake value ratios to establish PIB‐positive (PIB+) cutoff. Results The five patients with late‐onset SD were PIB‐negative. Two of six with early‐onset SD, seven of nine with AD, and 1 of 10 controls were PIB+. The SD participants who were PIB+ did not have memory or visuospatial deficits that are typical in AD. Conclusions Aβ deposition does not seem to be associated with late‐onset SD. Future larger studies might confirm whether a significant minority of early‐onset SD patients exhibit Aβ deposition. Copyright © 2016 John Wiley & Sons, Ltd.